Personalized Cancer Vaccines

Although immunotherapy has been around since the late 1800’s with William Coley injecting tumors with live attenuated strains of Streptococcus pyogenes and Serratia marcescens, it went on the back burner as a treatment method due to fears of infecting immunocompromised individuals. It wasn’t until 1976 that immunotherapy once again became mainstream with the use of Bacille Calmette-Guérin (BCG) for the treatment of bladder cancer.

The 1990s saw a huge increase in immunotherapies. The well-known IL-2 treatment, approved by the FDA for metastatic kidney cancer in 1991 and for metastatic melanoma in 1998, works by stimulating the body’s own T-cell production. Monoclonal antibodies were approved for use in the treatment of non-Hodgkin’s lymphoma in 1997. Work on cancer vaccines, using cloned antigens to activate cytotoxic T cells began in 1991, but the FDA didn’t give the first approval to a cancer vaccine until 2010 for the use in castration resistant prostate cancer.

A new day is dawning in cancer vaccines, with the use of neoantigens for the treatment of certain cancers. Plainly put, when cancers mutate, they can express new antigens – thus the term neoantigen – that present the opportunity for a person’s own body fight the cancer. All we need is a way to encourage the immune system to recognize these antigens and fight away! Recent research is showing a promising future for this new model of cancer therapy. Last May, Sanford, et al, released preliminary results of an ongoing Phase II trial. Sixteen patients previously treated with BCG, who experienced recurrent urothelial carcinoma were randomized into two treatment arms: one BCG treatment only, and one with BCG and a cancer vaccine (PANVAC) that contains three tumor-specific antigens. Excitingly, those patients in the BCG+PANVAC arm exhibited statistically significant increases in immune response over those in the BCG only arm. Researchers at Harvard and the Dana-Farber Cancer Institute have hopefully provided an answer to that needed delivery method. Building on previous research from completed at Harvard in 2014, they devised a method of coating mesoporous silica rods (MSRs) with polyethyleneimine (PEI). It was found that when they load these PEI coated MSR scaffolds with neoantigens specific to tumors, stimulation of dendritic cells was significantly enhanced. In vivo studies in mice showed the ability to “eradicate large tumors and tumor metastases, create a memory of tumors enabling future tumor rejections and… restimulate fading anti-tumor immunity in cancer patients.”

Could these personalized vaccines be the golden key in cancer treatment? Perhaps. Only time will tell. But it is surely an exciting time to be in the research community!

Image: esbenh ©