Optogenetic immunomodulation for adoptive cell transfer therapy



 DESCRIPTION (provided by applicant): T cell-based immunotherapy utilizing adoptive cell transfer (ACT) of tumor-targeting cytotoxic T lymphocytes (CTLs) has emerged as a powerful treatment option for several types of cancer patients. However, tumors undergo immunoediting, resulting in the selection of tumors that have established either a favorable microenvironment that facilitates their growth or an immunosuppressive environment that enables them to avoid immune destruction. Despite promising successes in the clinic, impaired trafficking of CTLs to tumor sites, strong immunosuppressive tumor microenvironment, and off-target cytotoxicity are main barriers to achieving the maximum benefits of ACT therapy. Optogenetics is a technique that uses a combination of techniques from optics and genetics to control defined cellular processes by controlling genetically modified light-sensitive proteins using optical stimulation. I this study, we will use several novel optogenetic techniques to, (1) improve trafficking of CTLs to tumor sites, (2) overcome strong immunosuppressive tumor microenvironment, and (3) prevent off-target cytotoxicity. The use of light to control immune reactions avoids the need for direct physical contact with the tissue and, therefore, any interference with normal functions. Importantly, light offers outstanding spatial resolution, allowing access to specific cellular subtypes and even the smallest subcellular domains. Clinically, ACT therapy is also a common treatment modality for various cell therapies. Thus, our novel optogenetic approach may have broad applications not only for anti-tumor immunotherapy but also for potential therapies that are not limited to leukocytes or anti-tumor settings.