Scientists Discover New Vaccine Approach To Treat Cancer

• Scientists have discovered a new approach for treating cancer based on manipulating the immune response to malignant tumors.
• And the team at Trinity College Dublin, Ireland, led by Professor Kingston Mills, Professor of Experimental Immunology, have also developed a new vaccine to treat cancer at the pre-clinical level. 
• The discovery has been patented and there are plans to develop the vaccine for clinical use for cancer patients. 
• The first cancer vaccine Sipuleucel-T (Provenge(tm)) was licensed last year for use in prostate cancer patients unresponsive to hormone treatment. 
• Unfortunately, this cell-based vaccine only improves patient survival by an average of 4.1 months. 
• Vaccines for infectious diseases are highly effective at generating immune responses that prevent infection with bacteria or viruses. The immune system can also protect us against tumors and in theory a vaccine approach should be effective against cancer. 
• In practice this has proven very difficult because unlike infectious diseases, tumors are derived from normal human cells, and not made up of foreign substances or antigens capable of triggering an immune response. 
• The tumors instead produce molecules that suppress the efficacy of the immune system. They generate regulatory cells that inhibit the immune response that could potentially clear the tumors. 
• Professor Mills' group has developed a novel vaccine and immunotherapeutic approach that can overcome these obstacles and has the potential to significantly improve on existing technologies. 
• The therapy is based on a combination of molecules that manipulates the immune response to curb the regulatory arm while enhancing the protective arm, allowing the induction of specialist white blood cell called killer T cells to target and eliminate the tumors. The new vaccine approach was found to be highly effective at pre-clinical stage in treating a range of cancers in murine models. 

The findings were published in December online in Cancer Research entitled
Original article: Effective treament of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy.

Authors: Corey Smith, Janice Tsang et.al 

Abstract
Nasopharyngeal carcinoma (NPC) is endemic in China and Southeast Asia where it is tightly associated with infections by Epstein-Barr virus (EBV). The role of tumor-associated viral antigens in NPC render it an appelaing candidate for cellular immunotherapy. In earlier preclinical studies, a novel adenoviral vector-based vaccine termed AdE1-LMPpoly has been generated that encodes EBV nuclear antigen-1 (E1) fused to multiple CD8+ T cell epitopes from the EBV latent membrane proteins LMP1 and LMP2. Here we report the findings of a formal clinical assessment of AdE1-LMPpoly as an immunotherapeutic tool for EBV-associated recurrent and metastatic NPC. From a total of 24 NPC patients, EBV-specific T cells were successfully expanded from 16 NPC patients (72.7%), while 6 NPC patients (27.3%) showed minimal or no expansion of virus-specific T cells. Transient increase in the frequencies of LMP1/2 and EBNA1-specific T cell responses was observed after adoptive transfer, associated with grade I flu-like symptoms and malaise. The time to progression (TTP) in these patients ranged from 38-420 days with a mean TTP of 136 days. Compared to patients who did not receive T cells, the median overall survival increased from 220 to 523 days. Taken together, our findings demonstrate that adoptive immunotherapy with AdE1-LMPpoly vaccine is safe and well tolerated and may offer clinical benefit to NPC patients.
by
Akshaya Srikanth
Pharm.D Internee

Hyderabad, India