IMV, Wistar Institute Partner to Develop T-cell Immunotherapy Against Cancers with BRAF Mutations

IMV announced that it has joined with the Wistar Institute to develop an immunotherapy targeting cancer cells with mutations in the BRAF gene. Such mutations are linked to some types of ovarian and other cancers.

Under the partnership, IMV will use its proprietary DPX drug delivery platform to design an immunotherapy using small molecules provided by the Winstar Institute. The molecules mimic the abnormal BRAF protein, and activate T-cells against cancer cells carrying mutated BRAF proteins.

“We are pleased to initiate this collaboration with The Wistar Institute, a world leader in biomedical research and early-stage discovery science with highly relevant expertise to our shared goals in the development of novel treatments for cancer,” Frederic Ors, IMV’s CEO, said in a press release.

The BRAF gene holds the instructions to produce a cell surface protein with the same name. The protein controls a number of important cell functions, including growth and division, differentiation, migration, and programmed cell death.

Mutations in this gene, however, lead to the production of a faulty protein that promotes cancer by letting cells proliferate and migrate without control. They are most frequently found in melanomas, but have also been identified in ovarian cancer, lymphoma and other cancers.

“Small-molecule inhibitors of BRAF have shown to be very effective targeted cancer therapies, but with limited long-term benefit due to the onset of therapy resistance. Alternative strategies with emerging therapeutic approaches are needed for the successful long-term treatment of cancers with the BRAF mutation,” said Meenhard Herlyn, a professor in the Molecular and Cellular Oncogenesis Program and director of Wistar’s Melanoma Research Center.

“Immunotherapy could provide a more effective mechanism to target these mutations, and we are excited to collaborate with IMV, as its DPX technology enables us to develop targeted T cell therapies aimed at BRAF to test and validate this important hypothesis,” he added.

The potential new therapy aims to combine small fragments of the BRAF protein — identified by Herlyn and his team  — and the DPX technology to achieve a longer lasting and specific response.

DPX is a drug delivery system. Injected under the skin, it works to increase the immune response against cancer cells carrying the target molecule — in this case, the BRAF protein — by recruiting T-cells to the tumor site.

“We believe that cancer-driving mutations, like BRAF, which are directly involved in malignant processes and do not easily escape the immune system, represent an exciting new avenue for targeted T cell therapies,” Ors said.

IMV’s leading investigational treatment, DPX-Survivac, a T-cell-activating immunotherapy targeting survivin (a cancer biomarker associated with poor prognosis) is currently being tested as a monotherapy and in combination with other treatments in women with advanced ovarian cancer.

Early results of the DECIDE1 Phase 1/2 trial (NCT02785250) support the therapy’s potential to generate a significant anti-tumor response.