Engineering cellular immunotherapies
Clinical trials have shown that chimeric antigen receptor (CAR)-T cells can selectively bind to a surface protein found on only antibody producing cells (B cells) and on B cell cancers (leukemias). Patients who receive such CAR-T cells often show complete remission of their leukemias as well as a dramatic loss of their normal B cells. In addition to eliminating normal B cells, CAR-T cell therapies can also lead to life-threatening toxicities (e.g. cytokine storm) for some patients. Moreover, CAR-T cell therapies have not yet shown clinical benefit for patients with solid tumors partly because most surface proteins expressed on tumors are also expressed on normal tissues required for viability and partly because solid tumors often have very potent strategies to limit immune attack against them.
We are engineering tools that broaden the application of CAR-T cells to attack solid tumors. We have engineered CAR T cells that bind to small molecules rather than directly to tumors. By conjugating these small molecules to antibodies, CAR T cell activities can be dosed by modulating the timing, dose and route of administration of the antibody-small molecule conjugates. Moreover, CAR T cell activities can be re-directed by using multiple antibodies each conjugated to different targets. This CAR system is universal in that it can be used for multiple indications and different cell types. We are working with clinical and industry collaborators to engineer CAR-T cells for Dana-Farber patients.
We are engineering tools that broaden the application of CAR-T cells to attack solid tumors. We have engineered CAR T cells that bind to small molecules rather than directly to tumors. By conjugating these small molecules to antibodies, CAR T cell activities can be dosed by modulating the timing, dose and route of administration of the antibody-small molecule conjugates. Moreover, CAR T cell activities can be re-directed by using multiple antibodies each conjugated to different targets. This CAR system is universal in that it can be used for multiple indications and different cell types. We are working with clinical and industry collaborators to engineer CAR-T cells for Dana-Farber patients.
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