Unleashing the Potential of ALLO-316: A CD70-Targeted Allogeneic CAR T-Cell Therapy for Acute Myeloid Leukemia

CD70, a glycoprotein from the TNF family, is crucial for the survival and differentiation of activated T cells into effector and memory cells. It is typically found in limited quantities in normal tissues, such as in activated lymphocytes and mature dendritic cells, but is more prevalent in various cancers like renal cell carcinoma and acute myeloid leukemia. This makes CD70 a promising target for cancer treatment.

The innovative strategy of using chimeric antigen receptor (CAR)-modified T cells has shown significant potential in treating blood cancers, with the success of CD19-targeting therapies like Kymriah and Yescarta paving the way for further exploration. Our research has identified a potent allogeneic CAR T cell candidate against CD70, which has demonstrated strong efficacy against renal cell carcinoma both in vitro and in vivo.

In the context of acute myeloid leukemia, we have evaluated the presence of CD70 on AML cell lines and patient samples, with a majority of samples exhibiting considerable CD70 expression. We have also successfully created CD70-targeting allogeneic CAR T cells, which did not express CD70 themselves post-generation, possibly due to fratricide or CAR-induced "masking" effects.

To enhance safety and efficacy, gene-editing techniques have been employed to modify the T cells, reducing the risk of graft-versus-host disease and providing resistance to an anti-CD52 antibody used in conditioning regimens. The modified CAR T cells, ALLO-316, have shown remarkable effectiveness in eliminating CD70-expressing target cells and have demonstrated anti-tumor activity in an in vivo model.

Furthermore, we have conducted toxicity assessments, finding no CD70 expression on normal hematopoietic progenitor cells, which suggests that the treatment could be safe and specific to cancer cells. Our findings indicate that CD70 allogeneic CAR T therapy is a viable option for the treatment of AML and warrants further clinical investigation.