1. Presenters: Maria Maqsood ξ Sania Munir Cancer Immunotherapy

2. Cancer immunotherapy Proffered over surgery, radiation and chemotherapy. WHY??

3. Cancer Immunotherapy specificity of immune mechanisms could be harnessed against tumor cells. This might use: the patient's own immune system (immunostimulants) the transfer of – antibodies (i.e. passive immunization) or – T cells from an outside source.

4. Immunostimulants T cells are present in cancer patients. Immune surveillance fails here. So immunostimulants are being used: – injection of adjuvant like agents – interleukin-2 – alpha-interferon

5. Cancer Therapy with Monoclonal Antibodies monoclonal antibodies show promise against cancer, especially cancers of white blood cells (leukemias, lymphomas, and multiple myeloma).

6. Rituximab (trade name = Rituxan®): Used to treat B-cell lymphomas. Herceptin®: Binds HER2, a growth factor receptor found on some tumor cells (some breast cancers, lymphomas). Alemtuzumab (MabCampath®): Binds to CD52, a molecule found on white blood cells.

7. Lym-1 (Oncolym®): Binds to the HLA-DR- encoded histocompatibility antigen that can be expressed at high levels on lymphoma cells Bevacizumab (Avastin®): Binds to vascular endothelial growth factor (VEGF) thus blocking its action and depriving the tumor of its blood supply.

8. Cetuximab (Erbitux®): Used to treat colorectal cancers. Ipilimumab (Yervoy®): Blocks the immunosuppressive effects of CTLA-4 (thus a double-negative).

9. Immunotoxins It should have two parts: – monoclonal antibody specific for the cancer cell attached to – a cytotoxic drug or toxin that kills the cell once it gets inside. Only one has been approved by FDA yet.

10. Immunotoxins Adcetris®: a conjugate of a: – monoclonal antibody that binds CD30 – vedotin, a drug that blocks mitosis by preventing the polymerization of tubulin (needed to form the mitotic spindle).

11. Immunotoxins The vedotin is attached to the monoclonal antibody by a bridge that is cleaved once the conjugate is safely inside the tumor cell releasing the toxin to do its work there. In one trial, 73% of the patients with Hodgkin's lymphoma went into remission.

12. Radio immunotherapy Monoclonal antibodies against tumor antigens can also be coupled to radioactive atoms. The goal with these agents is to limit the destructive power of radiation to cancerous cells.

13. Radio immunotherapy Zevalin®: This is a monoclonal antibody against the CD20 molecule on B cells (and lymphomas) conjugated to either – the radioactive isotope indium-111 (111In) – Or – the radioactive isotope yttrium-90 (90Y).

14. Radio immunotherapy Bexxar® (tositumomab). This is a conjugate of a monoclonal antibody against CD20 and the radioactive isotope iodine-131 ( 131 I). On 3 February 2005, the New England Journal of Medicine reported that 59% of patients with a B- cell lymphoma were disease-free 5 years after a single treatment with 131 I-tositumomab (a treatment that was relatively free of the nasty side-effects, e.g., hair loss, of conventional chemotherapy).

15. Cancer Vaccines The purpose of cancer vaccines is to elicit a more powerful active immunity in the patient. Patient specific cancer vaccines are being made. – Dendritic-Cell Vaccines – Patient-Specific Tumor Antigen Vaccines

16. Tumor-Antigen-Specific Vaccines These vaccines are used to immunize the patient with an antigen universally expressed by tumors of that type (but not by normal cells) mixed with some form of adjuvant that will enhance the response. Example is: – MAGE-A3 is a protein common on cancer cells. A vaccine using MAGE-A3 — along with an adjuvant — is in Phase III clinical trials to assess its effectiveness against melanoma and lung cancer.