Cancer is a leading cause of death in the developed world, and has historically been treated with surgery, radiation therapy, and chemotherapy, which use nonspecific mechanisms to attempt to remove or to kill cancer cells. More recently, therapies have focused on harnessing the immune system to fight cancer. Cancer is famous for its ability to deceive, appearing to the immune system as normal tissue while wreaking destruction on the body. Vaccines consisting of neoantigens mobilize the immune target to target the tumor cells. Earlier cancer immunotherapy drugs targeted antigens that also can be expressed in normal cells, making healthy tissues potentially vulnerable to an immune response.
Frame therapeutics is dedicated to transforming the treatment of cancer by directing the immune system towards frame neoantigens. Neoantigens arise from somatic mutations that differ from wild-type antigens and are specific to each individual patient, which provide tumor specific targets for developing personalized cancer vaccines. We focus on antigens that are shared, as a result of frame shifts, to provide them off the shelf. The presence of neoantigens in cancer cells and their absence in normal cells makes them compelling, untapped targets for cancer therapy. By directing the immune system towards these targets, our neoantigen-targeted therapies will offer a new level of patient and tumor specificity in the field of cancer immunotherapy. Personalized neoantigen vaccines represent a potential new class of cancer immunotherapy.
Each tumor expresses a unique set of neoantigens. The idea of a vaccine is to arouse the body’s response to neoantigens, and to teach it to target neoantigens that it did not respond to before.
Neoantigen-targeted therapies are different to other attempts to provide the immune system with a target because many prior efforts focus primarily on ‘tumor-associated antigens’ which, unlike neoantigens, are not specific to the tumor and are also found in normal cells. The exclusive specifity and possibility to use it broadly across different cancer types, give neoantigen-targeted therapies a potential significant benefit over targeting tumor-associated antigens.
From analysis of tens of thousands of DNA-sequenced tumors it is clear that (with the rare exception of some Ras and Raf mutation) there are virtually no common mutations that are shared between individual tumours. Therefore, personalised neoantigen vaccination thus depends on the de novo synthesis of vaccines each time after the patients tumor DNA has been sequenced. This is time consuming, it is costly since it is hardly scalable, the efficacy of that particular neoantigen can never be fully predicated and regulatory supervision on the manufacturing and admission requires attention.
We discovered that a subset of the mutation in tumours, frame shifts, do result in common shared antigens, so that vaccines can be prepared, stored, and provided off-the-shelf to doctor or patient, on demand.
The focus of the company is to produce (in strategic collaboration with others when necessary) immunotherapeutics based on these 'Frames' (peptide sequences shared among different tumors as result of frame shifts). They are presumably strong antigens, entirely novel, thus no need for prediction of MHC match, and with the advantages of scale and time gained by providing off the shelf.
Frame Therapeutics focuses on the highly immunogenic neoantigens that occur in tumors, namely novel peptides resulting from frameshift mutations. The basis for our method is the discovery that there are (almost) no common mutations in cancers, but that different mutations can bring into frame common antigens, and do so at levels that enable production of off the shelf vaccines.