Immunotherapy

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What is immunotherapy?

• Treatment that uses certain parts of the immune system to fight diseases such as cancer

• Stimulating your own immune system to work harder or smarter to attack cancer cells

• Giving you immune system components, such as man-made immune system proteins

• Dr William Coley used Coley's Toxins in the late 1800s as crude immunotherapy with some success.

• first therapeutic monoclonal antibodies rituximab (Rituxan) and trastuzumab (Herceptin) were approved during the late 1990s to treat lymphoma and breast cancer

Immune Response to Tumors

Types of immunotherapy• Passive immunotherapy:• Adminstration of monoclonal antibodies which

target either tumour-specific or over-expressed antigens.

• Active immunotherapies:• Cytokines- IL-2 / IFNs / TNFα • Cancer vaccines• Cell-based therapies• tumour-specific CTL• tumour-derived APC• DC priming

Monoclonal antibody therapy

• monoclonal antibodies that bind only to cancer cell-specific antigens and induce an immunological response against the target cancer cell.

• Naked mAbs :antibodies that work by themselves. boost a person’s immune response against cancer cells.

• blocking specific proteins that help cancer cells grow. Eg. Trastuzumab-HER2

• Conjugated mAbs: are those joined to a chemotherapy drug, radioactive particle, or a toxin

• Radiolabelled: Ibritumomab tiuxetan and tositumomab –CD20Ag

• Chemolabeled: brentuximab vedotin -CD30 antigen• Immunotoxins: denileukin diftitox

Monoclonal antibodies for cancer. ADEPT, antibody directed enzyme pro drug therapy; ADCC, antibody dependent cell-mediated cytotoxicity; CDC, complement dependent cytotoxicity; MAb, monoclonal antibody; scFv single-chain Fv fragment

Cancer vaccines• Tumor cell vaccines: made from actual cancer cells that

have been removed during surgery.• Antigen vaccines: These vaccines boost the immune

system by using only one antigen rather than whole tumor cells

• Dendritic cell vaccines: special immune cells in the body that help the immune system recognize cancer cells

• DNA vaccines: Vectors can be given bits of DNA that code for protein antigens.

• When the vectors are then injected into the body, this DNA might be taken up by cells and can instruct them to make specific antigens

Mechanism of action of Sipuleucel T ‑

Adoptive immunotherapy for cancer

vemurafenib

Dendritic Cell based Immunotherapy

cytokine based cancer therapy

Other drugs that boost the immune system• Thalidomide: • treatment for multiple myeloma• Lenalidomide:• Newer drug , treatment for multiple myeloma• Bacille Calmette-Guérin:• treatment of superficial forms of bladder cancer• Colorectal cancer• Lung cancer• Melanoma• Medicinal mushrooms:• Agaricus subrufescens -anticancer properties

Reference

• Kantoff PW, Schuetz TJ, Blumenstein BA, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28:1099-1105.

• Recent Advances and Current Challenges inTumor Immunology and Immunotherapy

• Text books:• The biology of Cancer:R.A Weinberg 2nd ed• Kuby Immunology 8th ed• Ivan roitt Essential Immunology 12th ed

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