ALLO-647 Integration in Lymphodepletion: Paving the Way for Enduring Responses and Safe CAR T cell Therapy Advancements

Despite the rising clinical fascination with autologous CAR T-cell therapies for hematologic malignancies and their noteworthy achievements, persistent challenges revolve around logistical issues, manufacturing constraints, variations in quality consistency, and the ongoing struggle to ensure product availability. 

The success of allogeneic CAR T cells hinges on the development of a secure and efficient method to manage the host lymphocyte rejection of these cells, known as allo-rejection. ALLO-501 and ALLO-501A represent allogeneic anti-CD19 CAR T-cell products, utilizing Cellectis technologies’ TALEN gene editing to disrupt both the TCRα constant (TRAC) and CD52 genes. Specifically, the disruption of CD52 allows for the use of ALLO-647, facilitating the transient and selective depletion of host lymphocytes. This strategic approach enables ALLO-501 and ALLO-501A to thrive post-infusion, avoiding swift allo-rejection and opening new avenues for effective treatment. The comprehensive safety assessment, encompassing all 87 Phase I patients undergoing treatment for both relapsed/refractory Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL), reveals that the addition of investigational ALLO-647 to standard lymphodepletion is a safe approach. This strategy creates a favorable window for the expansion and enduring presence of AlloCAR T cells, holding the promise to instigate profound and long-lasting remissions in cases of relapsed and treatment-resistant cancers. Furthermore, no unexpected safety concerns were observed. Neutropenia and anemia were the most common any-grade treatment-emergent adverse events (or TEAEs) and neutropenia, anemia, and thrombocytopenia were the most common Grade 3 or higher TEAEs.

In November 2023, the company obtained Fast Track Designation (FTD) for the application of ALLO-647 in adult patients experiencing relapsed or refractory Large B-cell lymphoma.

 KOL insights

“We believe in the immense potential of off-the-shelf CAR T products to not only address the limitations of current autologous CAR T cell therapy but to also provide greater access to patients in need. We fully understand the importance of lymphodepletion to achieving optimal outcomes, and ALLO-647 is just the first generation of our innovative approaches to enhancing lymphodepletion to promote expansion of CAR T cells.” –Expert Opinion.

Conclusion

A thorough examination of all participants in the Phase I ALPHA/ALPHA2 trials reveals that the incorporation of investigational ALLO-647 into standard lymphodepletion not only results in sustained responses but also maintains a safety profile on par with approved autologous CAR T therapies. This comprehensive analysis underscores the potential of ALLO-647 as a promising and safe addition to existing therapeutic approaches in the field.

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