On April 13, 2023 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company discovering and developing innovative gamma-delta T cell therapies, reported positive preclinical data for its novel non-signaling CAR (nsCAR) platform and the launch of its INB-330 program in AML (Press release, In8bio, APR 17, 2023, View Source [SID1234630159]). The new data included preliminary results for the nsCAR platform targeting CD33, a challenging but potentially impactful target in AML. The data were presented in a poster session (abstract #1777) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023.
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"The pairing of an nsCAR with the innate killing ability of gamma-delta T cells has the potential to become a cornerstone in the treatment of both solid and liquid cancers, given the increased anti-tumor efficacy and preservation of healthy cells," remarked William Ho, CEO and co-founder of IN8bio. "IN8bio’s unique knowledge of the biology and manufacturing of gamma-delta T cells positions it as a leader in next generation CAR platforms for the treatment of previously undruggable targets."
IN8bio’s nsCAR platform is based on the natural ability of gamma-delta T cells to distinguish between healthy and malignant tissue. By using a CAR that lacks a signaling domain, IN8bio believes it has created a technology that enables these cells to differentiate between tumor and healthy tissue, even when both express the CAR-targeted antigen. The power of the nsCAR technology to selectively target tumor cells was shown in proof-of-concept studies against the validated target of CD19. Preliminary data showed a gamma-delta CD19 nsCAR (ns19CAR) killed 80% of leukemia cells versus only 5% of healthy B cells, which both express the CD19 target.
The new data presented at AACR (Free AACR Whitepaper) includes early preclinical results for the INB-330 program targeting CD33 for AML, an important but challenging target due to its expression on both leukemic cells and hematopoietic stem cells (HSCs). Previous therapies targeting CD33 were limited due to the significant side effects resulting from the unintended targeting of these HSCs. The data presented at AACR (Free AACR Whitepaper) showed that a CD33 targeting nsCAR construct (ns33CAR) was successfully engineered into gamma-delta T cells. The ns33CAR cells were able to distinguish
between leukemic cells and healthy monocytes isolated from peripheral blood, both of which express CD33. The ns33CAR demonstrated anti-leukemic activity against AML, B-cell acute lymphoblastic leukemia (B-ALL), and chronic myeloid leukemia (CML) cell lines. These preliminary findings support the ongoing evaluation of INB-330 in AML and improvements in transduction and CAR optimization are ongoing.
"We are thrilled to present this promising preclinical data from our next-generation nsCAR platform, which shows the potential of our INB-300 platform and INB-330 program to differentiate between cancerous and healthy tissue," said Lawrence Lamb, Ph.D., co-founder and Chief Scientific Officer of IN8bio. "Our goal is to improve upon existing technologies with a targeted but potentially less toxic approach for patients who require more innovative therapies. The ability of this platform to avoid on-target off-tumor killing also allows us to explore previously "undruggable" targets in complex diseases such as AML and solid tumors. We are encouraged by these results and look forward to seeking potential partners and further evaluating the nsCAR platform with additional targets."
About INB-300
INB-300, is a non-signaling CAR (nsCAR) gamma-delta T cell platform, with several preclinical product candidates, including the INB-330 program against AML targets, that combine our expertise in gamma-delta T cells and genetic engineering. These nsCAR constructs lack signaling domains in order to take advantage of the unique properties of gamma-delta T cells to differentiate between healthy and tumor tissues. IN8bio is advancing new nsCAR constructs against multiple targets to treat both solid and liquid tumors.