Towards a Platform for Cost-Effective Personalized Cancer Immunotherapy, Tailored to the Patient and Tumor

If you live long enough, you will get cancer. It's just a matter of time and odds, and thus any future rejuvenation toolkit must include robust medical technology capable of curing cancer. The principal challenge of cancer research is that every tumor has a different biochemistry, different enough to cause great variation in the effectiveness any one narrow strategy based on targeting a single protein or cellular process. Ways around this issue include (a) focusing on one of the few mechanisms that are the same in all cancers, such as the need to lengthen telomeres, and (b) developing some means to cost-effectively target a different set of proteins and mechanisms in every cancer patient. This early-stage research takes the second approach:

A tailored immunotherapy approach that could be used as a "universally applicable blueprint" was found to be effective in three independent tumour mouse models, a new study reports. Tumour-specific mutations represent ideal targets for cancer immunotherapy as they lack expression in healthy tissues and can potentially be recognised by the body's immune system. However, systematic targeting by vaccine approaches have been hampered by each patient's tumour possessing a unique set of mutations - the mutanome - that must be identified first.

In the current study, researchers established a process by which mutations identified by exome sequencing could be selected as vaccine targets through bioinformation prioritisation based on both expression levels and major histocompatibility complex (MHC) class II-binding capacity for rapid production. The team undertook work on three separate mouse models of lung, skin, and colon cancer. The investigators generated vaccines that delivered customised synthetic mRNA sequences which encouraged CD4 T cells to attack the target mutations, and showed improved survival in mice treated with the vaccines compared to untreated mice. Finally, they demonstrated an abundance of mutations predicted to bind to MHC class II in human cancers by employing the same predictive algorithm on corresponding human cancer types.

"The tailored immune-therapy approach introduced here may be regarded as a universally applicable blueprint for comprehensive exploitation of the substantial neo-epitope target repertoire of cancers, enabling the effective targeting of every patient's tumour with vaccines produced 'just in time.'"

Link: http://ecancer.org/news/7219-mouse-models-show-tailored-immunotherapy-to-be-effective.php