Abstract 3588: ACTallo: A novel approach using gamma-delta T cells to allogeneic cellular therapy to treat cancer

Adoptive cellular therapy (ACT) has dramatically changed the landscape of cancer immunotherapy; however, the complex manufacture of individualized products from late-stage, heavily pre-treated cancer patients, together with high cost-of-goods, encourages the development of simpler ‘off-the-shelf9 alternatives. The unique properties of γδ (gamma-delta) T cells make them a seductive candidate for effective allogeneic ACT. In contrast to αβ T cells, γδ T cells are endowed with intrinsic antitumor activity while unable to induce graft-versus-host disease. γδ T cells have a high proliferative potential before exhibiting exhaustion. Moreover, in the context of αβ TCR-engineered ACT, γδ T cells pose a lesser risk of off-target toxicity, due to the absence of expression of endogenous αβ TCR and hence, risk of mispairing with the engineered αβ TCR. Here, we will present the ACTallo® platform, which combines the unique properties of γδ T cells with Immatics9 XPRESIDENT ® target/TCR discovery platform. The ACTallo® process selectively expands Vγ9Vδ2 T cells that are retrovirally-transduced to co-express CD8 together with a tumor-specific αβ TCR. Over a period of 45 days or less, ACTallo® γδ T cells can expand >30,000 fold. γδ T cells obtained this way recognize tumor cells, express cytokines, degranulate and kill tumor cells specifically. In addition, ACTallo® γδ T cells show no signs of exhaustion after expansion, as evidenced by the lack of expression of PD1, TIM3 or LAG3. ACTallo® is intended to overcome the limitation of autologous cellular therapies towards off-the-shelf approach, by combining the large-scale expansion potential of allogeneic γδ T cells with novel TCRs against XPRESIDENT ® mass-spectrometry guided tumor-specific targets. Citation Format: Mo Dao, Melinda Mata, Leonie Alten, Aleksandra Nowicka, Sabrina Kuttruff, Sarah Missel, Ali Mohamed, Toni Weinschenk, Yannick Bulliard, Steffen Walter. ACTallo: A novel approach using gamma-delta T cells to allogeneic cellular therapy to treat cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3588.