Trends in Biotechnology

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Trends in Biotechnology

• Medical Biotechnology

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• Brief Outline
• Gene Therapy
• Clinical Trials
• Recent Gene Therapy Success
• New Approaches to Gene Therapy
• Virotherapy
• Stem Cells
• Vaccines
• Tissue Engineering
• Xenotransplantation
• Drug Delivery

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• Brief Chapter Outline
•  

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• Gene Therapy
• Genetic Disorders
• Gene Target Selection
• Gene Delivery Methods
• Viral vectors
• Nonviral Delivery Methods
• Gene Therapy Examples

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• Clinical Trials
• Recent Gene Therapy Success
• New Approaches to Gene Therapy
• Spliceosome Mediated RNA Trans-splicing
• Triplex-Helix-Forming Oligonucleotide Therapy
• Antisense Therapy
• Ribozyme Therapy

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• Virotherapy
• Stem Cells
• Therapeutic Cloning and Embryonic Stem Cells
• Vaccines

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• Tissue Engineering
• Xenotransplantation
• Drug Delivery
• Biosensors
• Biotech Revolution Nanotechnology

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• Learning Objectives
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• Know how genetic diseases are generated and how
  genes are candidates for gene therapy.
• List and define the methods used to deliver genes
  into cells.
• Know the difference between ex vivo and in vivo
  gene therapy.
• List diseases that have been the subject of gene
  therapy research, the causes of those diseases,
  and how gene therapy attempts to treat them.
• Know the types of clinical trials and the steps
  of the clinical trial process required for gene
  therapy.

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• List and define new approaches to gene therapy,
  such as spliceosome-mediated RNA trans-splicing,
  triplex-helixforming oligonucleotide therapy,
  antisense therapy, and ribozyme therapy.
• Be familiar with the potential of stems cells,
  the types of stem cells used in research, and
  their applications. What are the issues
  surrounding the use of stem cells?
• Know the potential applications of biotechnology
  regarding vaccines, tissue engineering,
  xenotransplantation, drug delivery, and
  biosensors.

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• Gene Therapy

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• A. Introduction to Gene Therapy.
• Treat genetic diseases by putting normal genes
  into cells to correct a disorder. This is better
  than treating the disease with a drug that might
  not be a cure.
• Treat acquired and genetic diseases, eg cystic
  fibrosis and AIDS.
• Two types of gene therapy
• Somaticusing only the bodys cells to correct a
  disorder.
• Germ linepermanently modifying a gene in the
  reproductive cells.

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• Genetic Disorders.
• Medical problems caused by a mutation in one or
  more genes on the chromosomes. The person can be
  born with the mutation or develop it.
• Can be grouped into four categories

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• Can be grouped into four categories
• Single-gene
• Multigene disorders
• Mitochondrial disorders.
• Chromosome abnormalities.

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• Single-gene changesa mutation in one gene can
  result in a change in the protein product or
  possibly the elimination of the protein entirely.
  Sickle cell anemia is an example.

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• Multigene disordersalso called multifactor
  disorders, result from mutations in more than
  one gene, and sometimes along with environmental
  influences. Examples of these include heart
  disease, diabetes, and cancer.

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• Mitochondrial disordersaffecting many organ
  systems, these diseases are caused by mutations
  in mitochondrial DNA.

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• Chromosome abnormalitiescomplete chromosomes or
  large regions of a chromosome are missing,
  duplicated, or modified in some way. Down
  syndrome is an example.

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• Gene Target Selection.
• Usually, only a single gene causing a genetic
  disorder can be treated (candidates for treatment)

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• Gene Target Selection.
• The normal and mutated genes must be identified
  and well-studied.
• The disease caused by the mutation must be
  well-understood.
• An approved protocol involving a gene delivery
  method must be available.
• The potential toxic effects of the gene or gene
  delivery vehicle must be examined, as well as
  whether the therapy produces an immune response.

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• Gene Target Selection.
• The gene must be delivered to the correct cells.
• If the therapy method calls for it, the gene must
  be integrated into the host chromosome so the
  gene is not destroyed in host cells.
• The gene must be turned on (transcription) at the
  right time, and is also regulated properly.

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• .

Gene Major Delivery Methods for the insertion of
genes into cells. Ex vivo gene therapy In vivo
gene therapy
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• Gene Delivery Methods.
• Ex vivo gene therapy
• Cells are removed from the body.
• The gene of interest is inserted into them.
• The cells are cultured for reproduction.
• The cells are returned to the body.
• An advantage over in vivo gene therapy is that
  rejection does not occur if the persons own
  cells are used.
• The transplantation of the cells is the biggest
  technical problem.

• .

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• Possible in vivo engineering

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• Gene Delivery Methods.
• In vivo gene therapy
• The gene is inserted directly into cells within
  the body.
• Vectors such as viruses are used to target the
  DNA to specific cells.
• Technical difficulties
• The transferred gene is unstable and the product
  produced temporarily.
• The methods are not as controlled as ex vivo gene
  therapy because cells are not removed from the
  body.

• .

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Fig. 10.1 The different methods used to transfer
DNA into cells.
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• .

Viral Vectors (Figure 10.1). Retrovirus. Adenoviru
s. Adeno-Associated Virus.
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• .

• Viral Vectors
• Retrovirus.
• RNA viruses that only infect dividing human
  cells.
• DNA of interest can only be up to 8 kb in size.
• Site of integration into host chromosomes occurs
  randomly.
• Viral insertion could inactivate genes or elicit
  an immune response.

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• .

• Viral Vectors
• Adenovirus.
• Can infect dividing and non-dividing cells.
• Can engineer proteins on the virus surface to
  target specific cells.
• DNA of interest can be up to 7.4 kb and the
  protein will be highly expressed.
• Does not integrate into the genome, so there is
  low risk of mutation.

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• .

• Viral Vectors
• Adenovirus.
• Possible problems
• Temporary protein production because no
  integration occurs.
• The virus may replicate in host cells, killing
  them.
• Gene products may cause the cell to divide
  abnormally.
• The virus of gene products may cause an immune
  response.

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• Viral Vectors
• Adeno-Associated Virus.
• Infect dividing and non-dividing cells.
• Need a helper virus to infect host cells.
• DNA of interest can be up to 5 kb.
• 95 of the time DNA integrates into a region in
  chromosome 19, reducing the chance of genes being
  activated or inactivated by the insertion of DNA.

• .

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• Nonviral Delivery Methods.
• Other methods include
• electroporation,
• microinjection,
• biolistics (the gene gun), and
• liposomes (membrane-bound spheres that contain
  the DNA).

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• Gene Therapy Examples.
• First Gene Therapy.
• treatment of severe combined immune deficiency
  (SCID), (defective adenosine deaminase gene
  causes the immune system to not function
  correctly).
• 4-year-old girl received T-lymphocytes with the
  correct ADA gene.

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• The therapy had to be repeated - enzyme would be
  produced for only a few months.
• gt 50 of the T cells in the girl had the
  corrected gene, in 2003 her body still actively
  produces ADA.
• A second trial occurred on an 11-year-old girl,
  but her immune system developed a reaction
  against the virus, and only 0.1 to 1.0 of her
  cells produced ADA.

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• Lung DiseaseCystic Fibrosis.
• Caused by a defective ion transport molecule
  called the CF transmembrane conductance
  regulator (CFTR) in the plasma membrane of a
  cell (Figure 10.2).
• Affects airways, the intestines, and the pancreas
  
• People with CF have increased mucus production,
  bacterial infections in the lungs, and altered
  epithelial cell transport.

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Fig. 10.2 A drawing of the CFTR protein inserted
into the cell membrane.
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• For therapy to work, only a small amount of
  molecules need to be produced per cell. It has
  been successful in cell culture and in CF mice by
  liposomes.
• Spraying adenoviruses with the CFTR gene into the
  nose - only temporary treatment, and does not
  treat organs eg pancreas.
• Another alternative is spraying a DNA-liposome
  aerosol into the nose.

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• Liver Disease.
• Transfected hepatocytes (liver cells)
• Not very successful
• Only about 10 of the cells go into the liver.
• In 1992, a 29-year-old patient was treated for
  familial hypercholesterolemia (FH)
• Causes cholesterol to build up in arteries,
  leading to heart disease.

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• Caused by a defective low-density lipoprotein
  receptor (LDLR) gene.
• 250 grams of the patients liver was cultured.
• A retrovirus was used to infect about 25 of the
  cells.
• The cells put back into the liver.
• Tests confirmed that the cells were expressing
  the LDLR gene, and medication contributed to
  lowering cholesterol levels.

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• Clinical Trials.
• After the therapy has been tested on animals
  (called preclinical trials), it is then tried
  on humans.
• There are several types of clinical trials
• There are several phases to clinical trials
  (Figure 10.3)

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• There are several types of clinical trials
• Diagnostic trialidentifies better tests for
  diagnosing diseases.
• Treatment trialtests new therapies or drugs.
• Prevention triallooks for new ways to prevent
  disease in people who have never had the disease.
• Quality of life triallooks to improve the
  well-being and quality of life of chronically ill
  patients.
• Screening trialfinds ways to detect specific
  diseases or health conditions.

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• There are several phases to clinical trials
  (Figure 10.3)
• Phase I Trialstest on a small number (twenty to
  thirty) of human volunteers to find dosage
  limits, how to deliver it, and to find toxicity
  and safety.
• Phase II Trialsfind effectiveness and get more
  toxicity and safety information with a larger
  group of people (100300). If the therapy is
  effective and safe, the researchers begin phase
  III trials.

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• Phase III Trials many more people tested
  (10005000). Information obtained from phase I
  and II clinical trials is used, and the
  therapeutic role of the drug is studied.
• An application to the FDA is made for approval.
• Phase IV Trials after approval, if any
  questions remain regarding safety and efficacy,
  as well as the use of the treatment, they are
  studied in these trials before the drug is
  allowed to be released.

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Fig. 10.3 Drug discovery and approvals. (a) The
process of biotech drug discovery.
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Fig. 10.3 (b) New biotechnology drug and vaccine
approvals.
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• Recent Gene Therapy Success.
• No one has completely been cured by gene therapy,
  but small successes mean that gene therapy could
  be used for diseases that are difficult to treat.

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• Recent Gene Therapy Success.
• The first commercially licensed gene therapy
• In October 2003 in China, under the name
  Gendicine, after 5 years of clinical trials.
• Treats head and neck squamous cell carcinoma.
• An adenovirus vector containing the p53 tumor
  suppressor gene can be used along with
  chemotherapy and radiation therapy to increase
  effectiveness.
• Only reported side effect is a low-grade fever.

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• New Approaches to Gene Therapy
• Spliceosome Mediated RNA Trans-splicing
• Triplex-Helix-Forming Oligonucleotide Therapy
• Antisense Therapy
• Ribozyme Therapy

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• New Approaches to Gene Therapy.
• Why new approaches are needed
• Sometimes correcting the defective gene is not
  effective.
• For example, a mutated gene can prevent a normal
  protein from functioning properly. This is called
  a dominant negative gene and cannot be
  corrected by simply inserting the correct gene.

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Fig. 10.4 The effect of a dominant negative
mutation on a normal protein.
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• New Approaches to Gene Therapy.
• Spliceosome Mediated RNA Trans-splicing (SMaRT)
• Instead of correcting the gene, the region of
  mRNA that is affected is repaired
• An RNA strand that pairs with the intron (by base
  pairing) next to the mutated region (exon) of the
  mRNA is introduced into cells. The RNA is
  genetically modified to contain the correct exon
  and a small region that binds to the neighboring
  intron.

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• New Approaches to Gene Therapy.
• Spliceosome Mediated RNA Trans-splicing (SMaRT)
• Instead of correcting the gene, the region of
  mRNA that is affected is repaired
• When the RNA strand binds to the intron, the
  duplex (section of double-stranded RNA) causes
  the spliceosome to cut and remove the intron and
  the defective exon from the mRNA.
• The exons are joined, with the corrected exon
  ligated into the mRNA, thereby generating a
  functional, mature mRNA and protein.

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Fig. 10.5 A new approach to gene therapy using
spliceosome mediated RNA transplicing. (a) An
intron is excised from a normal transcript using
a spliceosome and exons 1 and 2 are ligated.
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Fig. 10.5 (b) In this example, a mutated exons 2
of the mRNA is repaired using SMART.
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• New Approaches to Gene Therapy.
• Triplex-Helix-Forming Oligonucleotide Therapy.
• triplex-forming nucleotides bind to target DNA
  regions, and block transcription into mRNA.
• The single-stranded string of nucleotides, about
  fifteen to twenty-one bases in length, binds to
  the groove between the double strands of DNA
  where the mutated gene is used.
• The triple helix that forms blocks transcription.
  
• A correct gene can be introduced into cells.

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Fig. 10.6 The prevention of transcription of mRNA
with a mutation using a triplex-helix-forming
oligonucleotide.
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• New Approaches to Gene Therapy.
• Antisense Therapy.
• Targets the mRNA of a mutated gene so that it
  cannot be translated into protein.
• Is complimentary to the mRNA that is used to code
  for the protein, called the sense mRNA.

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Fig. 10.7 A mutated mRNA cannot be translated
using antisense technology.
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• New Approaches to Gene Therapy.
• Antisense Therapy.
• The steps of the method are
• New, antisense RNA is introduced into cells
  that is complimentary to the mRNA that is used to
  code for the protein, called the sense mRNA.

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• New Approaches to Gene Therapy.
• Antisense Therapy.
• The steps of the method are
• The antisense RNA binds to the sense mRNA strands
  synthesized by the cell during transcription.
• The duplex RNA is blocked from translation into a
  protein, eliminating or dramatically reducing the
  production of a mutated protein.

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• New Approaches to Gene Therapy.
• Antisense Therapy.
• May be used to treat diseases where there is a
  loss of control over gene regulation or if a gene
  is overexpressed.
• The drug Genasense targets the mRNA for a protein
  called bcl-2. The protein is involved in the
  resistance of cancer cells to chemotherapy.

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Unfortunately

• Genta's stock took a nosedive yesterday on news
  that its lead drug Genasense, a Phase III
  candidate for melanoma, did not show a
  statistically significant benefit for its
  co-primary endpoint of progression-free
  survival.Read more Genta tanks on Genasense
  data - FierceBiotech http//www.fiercebiotech.com/
  story/genta-tanks-genasense-data/2009-10-29ixzz1x
  OC6H3X5 

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• New Approaches to Gene Therapy.
• Ribozyme Therapy.
• mRNAs that act as enzymes that can cut mRNA made
  by the cell.
• They exist naturally in cells and have roles in
  mRNA splicing (it is a part of the spliceosome)
  and the extension of the polypeptide during
  translation.

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• New Approaches to Gene Therapy.
• Ribozyme Therapy.
• The steps of this method are
• RNA is engineered to function as a ribozyme and
  to bind to the target mRNA.
• The ribozyme is introduced into cells.
• The ribozyme binds to the target mRNA encoded by
  the mutated gene.
• The target mRNA is cut, keeping it from being
  translated into protein.

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Fig. 10.8 Ribozymes are catalytic RNA that act as
enzymes to cut mRNA.
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Structure of hammerhead ribozyme
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• Virotherapy.
• Viruses can recognize and bind to a specific
  receptor on the host cell surface. Each virus can
  attach to a different receptor, so viruses have
  cell specificity.
• Viruses are engineered to infect and kill tumor
  cells, leaving normal cells intact.

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• Three different methods exist for virotherapy
• Infect, reproduce, and kill tumor cells. Viruses
  from the killed cells will then infect other
  cancer cells.
• Engineered viruses that have a tumor-specific
  promoter linked to an essential virus gene. The
  virus infects both normal and cancer cells, the
  gene turns on only in cancer cells and the virus
  kills the cancer cells.
• Engineered viruses that make tumor cells more
  susceptible to chemotherapy.

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• OncoVex attacks tumors in two ways. It features a
  modified cold sore virus that replicates inside
  solid tumors, causing cancer cells to die.
  Secondly, the drug prompts the immune system to
  take out cancer cells. In May 2009, BioVex
  released good Phase II data on the drug in
  melanoma patients. 13 patients had significant
  responses to the treatment, nine had signs of the
  cancer completely wiped out.Read more OncoVex
  - 10 promising late-stage cancer drugs -
  FierceBiotech http//www.fiercebiotech.com/special
  -reports/10-promising-late-stage-cancer-drugs/onco
  vex-10-promising-late-stage-cancer-drugsixzz1xOFS
  pdV0 

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• Stem Cells - About Stem Cells
• Genetically engineered undifferentiated stem
  cells may act as gene therapy agents.
• If stem cells containing a correct gene are
  inserted into a patient, the cells could divide
  and serve as a source of healthy cells to treat
  many diseases.

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• Scientists can isolate stem cells from a
  5-day-old mass of cells, called a blastocyst,
  that develops into an embryo. The cells are
  called embryonic stem cells and have the
  potential to develop into different cells of the
  body.

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• Goal of using stem cells is to treat damaged
  tissue by transplanting stem cells into a region
  of the body where they divide and differentiate
  into healthy tissue.

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Fig. 10.9 Stem cells obtained from bone marrow
can be cultured and induced to differentiate into
blood cells.
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• There are several types of stem cells
• Embryonic.
• Fetal.
• Umbilical cord blood.
• Adult.

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• Types of stem cells
• Embryonicthese cells are considered to be the
  most valuable type of stem cell because they can
  become almost any type of cell in the body. Can
  be obtained from in vitro fertilization (IVF)
  procedures.

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Fig. 10.10 Embryonic stem cells are obtained from
a blastocyst or embryo.
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• Types of stem cells
• Fetal - found in fetal brain tissue and are a
  natural source of dopamine neurons. Must come
  from prematurely terminated human fetuses or
  late-stage embryos. A human embryo is considered
  a fetus eight weeks after the egg is fertilized.
  Can possibly be used to treat Parkinsons disease.

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• Types of stem cells
• Umbilical cord bloodmultipotent stem cells. Even
  though they naturally become blood cells and
  immune system cells, they have the potential to
  become many different types of cells. Cause less
  rejection problems because they have not yet
  developed antigens that can be recognized by the
  immune system.

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• Types of stem cells
• Adult multipotent adult stem cells that develop
  into cells of a specific type of tissue. Believed
  to be the least flexible in being able to develop
  into any type of tissue. Research today is
  focused on trying to get these cells to become
  different cell types.

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• Most experiments involve cells that are in
  culture and are harvested from bone marrow,
  peripheral blood, and umbilical cord blood.

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• Using bone marrow stem cells can treat diseases
  such as leukemia because they develop into white
  blood cells, by killing all of the abnormal bone
  marrow and white blood cells and replacing them
  with donor stem cells, which replace the damaged
  marrow and cells.

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• Therapeutic Cloning and Embryonic Stem Cells.
• Can obtain stem cells from embryos cloned in a
  similar fashion to Dolly, the cloned sheep.

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• Therapeutic Cloning and Embryonic Stem Cells.
• Can obtain stem cells from embryos cloned in a
  similar fashion to Dolly, the cloned sheep.
• Performed in the following manner
• Nucleus is removed from an egg cell, and donor
  cells are extracted from the patient.
• Donor cells are cultured so that differentiation
  is reversed.
• Electrical pulse fuses the donor cell with the
  egg cell.
• The cell is induced to divide and form a
  blastocyst to extract stem cells from.
• Stem cells generated this way are not rejected
  because they are an exact genetic match to the
  donor.

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Fig. 10.11 Therapeutic cloning enables stem cells
to be produced that are genetically identical to
the donor patient.
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• Vaccines.
• New vaccines are being developed using new
  vaccine vectors and new delivery approaches,
  immunoenhancers, and nucleic acids.
• Vaccines are being developed against pneumonia,
  malaria, herpes virus, and others.
• New vaccines usually contain the antigen and not
  the organism.
• Small pieces of DNA from a microbe also induce an
  immune response, and are being studied to develop
  vaccines against malaria and HIV.

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• Tissue Engineering.
• Focuses on the development of substitutes for
  damaged tissues and organs.
• Combines biology and engineering to develop new
  tissue or the implantation of new cells.

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• Tissue Engineering.
• Occurs in the following way
• Tissue-inducing compounds, such as growth
  factors, serve as signals to stimulate the growth
  and development of new tissues.
• The cells reside within a natural or synthetic
  extracellular matrix that can be incorporated
  into a patients tissue. Scaffolds or networks of
  polymers may serve as a substrate for cell growth
  and formation into tissues.
• Isolated cells can be kept from host tissues to
  avoid rejection while they develop.
• When implanted in the body, blood vessels grow
  and provide nutrients.
• Stem cells can potentially be used for tissue
  engineering.

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• Tissue Engineering.
• Research has focused on transplanting functional
  pancreatic islet cells coated with alginates to
  treat diabetes. The cells are implanted into
  animals, and are linked to the bloodstream by a
  tube that prevents antibodies and white blood
  cells from making contact with the implanted
  tissue.

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• Tissue Engineering.
• A biohybrid kidney was developed that maintains
  kidney function until an injured kidney recovers.
  The kidney was made of hollow tubes seeded with
  kidney stem cells that divided until they lined
  the tubes and became functional kidney cells.

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Fig. 10.12 Tissue engineering offers hope to
hundreds of thousands of patients who need
functional tissues and organs. (a) Tobular
biodegradable scaffolds to from tubular tissue
such as veins, arteries, and intestines.
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Fig. 10.12 (b) Scanning electron micrograph of a
biodegradable polymer scaffold made of poly
(glycolic acid).
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• Scientists in London created an artificial
  windpipe which was then coated in stem cells from
  the patient.
• The technique does not need a donor, and there is
  no risk of the organ being rejected.
• A windpipe can be made within days.

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• 1 Trachea is removed from dead donor patient2 It
  is flushed with chemicals to remove all existing
  cells3 Donor trachea "scaffold" coated with stem
  cells from the patient's hip bone marrow. Cells
  from the airway lining added4 Once cells have
  grown (after about four days) donor trachea is
  inserted into patient's bronchus

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• Xenotransplantation.
• An organ or tissue transplanted from one species
  (such as a pig, baboon, or chimp) into another
  (such as a human) is a xenotransplant. An organ
  or tissue transplanted between two members of the
  same species (such as two humans) is an
  allotransplant. (Xeno is Greek for foreign allo
  is Greek for different).

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• Xenotransplantation.
• Tissue rejection, along with ethical and legal
  dilemmas, are major obstacles.
• Complement masking or shield proteins stop the
  complement system from attacking our own cells.
  Some transgenic animals can produce organs with
  the shield proteins on the surface.

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• Xenotransplantation.
• Pigs are the best possible organ donors. Their
  major organs are similar in size and shape to
  humans. Few diseases are transferred from pigs to
  humans.
• Pigs have been produced with shield proteins and
  may reach clinical trials.
• In 1999, 160 people received pig cells without
  bad reactions.

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• Drug Delivery.
• Why Good Delivery Systems Are Needed.
• Biosensors.
• Biotech Revolution Nanotechnology.

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• Drug Delivery.
• Why Good Delivery Systems Are Needed.
• Drugs are only useful if an effective method of
  delivery is available.
• Aerosols can be inhaled through the nose and pass
  into the lungs.
• A transdermal patch can transfer large peptides
  that do not normally diffuse through the skin
  into the skin and then into the bloodstream.

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• Drug Delivery.
• Biosensors.
• Biological components such as a cell, antibody,
  or protein and are linked to a very small
  transducer. The transducer receives the signal
  and transforms it into an understandable form.
• Transducers bind to the molecule, which produces
  an electrical or optical signal that can be
  detected.

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• Drug Delivery.
• Biosensors.
• Things that can be measured include blood
  components, environmental pollutants, toxins, and
  biological warfare agents.
• Nanotechnology may make biosensors so small that
  they can be easily concealed, or even placed into
  the body.

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• Drug Delivery.
• Biotech Revolution Nanotechnology.
• The study, manipulation, and manufacture of
  extremely small tools, structures, and machines
  at the molecular and atomic levels.
• A field that involves engineers, physicists,
  chemists, and molecular biologists.

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• Drug Delivery.
• Biotech Revolution Nanotechnology.
• Possible applications include
• Nanowiresvery small wires to transit
  electricity.
• Nanobotsrobots that assemble products.
• Nanomaterial productioncreate materials such as
  powders.
• Drug deliverytiny containers may deliver drugs
  to the correct places.
• DNA computersuse DNA as hardware and software.

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• Drug Delivery.
• Biotech Revolution Nanotechnology.
• Biological molecules may provide frameworks
  instead of material like silicon, to perform
  computing tasks such as mathematics.
• Scientists have demonstrated that 1000 DNA
  molecules can solve, in four months, complex
  problems that would take a computer 100 years to
  solve.

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Immunity and Cancer
Antibody
Macrophage
Cancer cell
Helper T cell
Natural killer cell
Cytotoxic T cell
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Immunotherapy
Radioisotope
Herceptin
Growth factor
Herceptin blocks receptor
Antibody
Antigen
Breast cancer cell
Lymphoma cell
Lymphoma cell destroyed
Growth slows
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Dendritic Cells That Attack Cancer
Dendritic cell matures and is infused back into
patient
Complex binds to dendritic cell precursor
Tumor antigen
T cell
Tumor antigen is linked to a cytokine
Complex is taken in by dendritic cell precursor
Dendritic cell displays tumor antigen and
activates T cells
Cancer cell
T cells attack cancer cell