John Gordon: ACTIVATE Platform Enhances Adoptive Cell Therapy for Solid Tumors
John Gordon, co-Founder, Director, VP Scientific Affairs at Celentyx Ltd, shared on LinkedIn about a recent paper by Anahita Nejatfard et al. published on BioRxiv:
“Cancer | Immunotherapy | ACTIVATE : A Modular Platform Orchestrating Coordinated Immune Responses to Improve Adoptive Cell Therapy Outcomes in Solid Tumors | Eric Appel & Co. ‘Get in on the ACT’ | Breaking at BioRxiv |
Adoptive Cell Therapy (ACT) has achieved curative responses in hematological malignancies, yet its translation to solid tumors remains limited by manufacturing bottlenecks, systemic toxicities, and poor T-cell infiltration and persistence within the immunosuppressive tumor microenvironment (TME).
Anahita Nejatfard, John Klich, Noah E., Sophia Bailey, Kyra Gillard, et al here* report the development and mechanism of ACTIVATE (Adoptive Cell Therapy and Immunostimulatory Vehicle for Anti-Tumor Efficacy), which leverages an injectable hydrogel depot technology that forms a transient inflammatory niche for localized co-delivery of adoptive T cells and native cytokines.
By tuning cytokine identity, ACTIVATE enables precise modulation of T-cell expansion, effector function, and interaction with endogenous immune networks. We found that enhancing T-cell proliferation alone is insufficient to drive robust tumor control; instead, coordinated engagement of both adoptive and endogenous immune responses is critical for durable anti-tumor efficacy.
In vivo, this orchestration via ACTIVATE led to enhanced infiltration and cytotoxicity of both adoptive and host-derived immune effectors, while driving robust recruitment and activation of T cells, B cells, dendritic cells, and macrophages in the tumor-draining lymph nodes.
This local immune activation can further reshape the TME, promoting antigen presentation and suppressing immunoregulatory populations, thus enhancing anti-tumor efficacy in a murine melanoma model.
These findings establish ACTIVATE as a modular platform for orchestrating coordinated immune responses to improve ACT outcomes in solid tumors.”
Title: A Transient Immunostimulatory Niche Synergizes Adoptive and Endogenous Immunity for
Enhanced Tumor Control
Authors: Anahita Nejatfard, John H. Klich, Noah Eckman, Sophia J. Bailey, Kyra Gillard, Daniel Ramos Mejia, Ben S. Ou, Jerry Yan, John W. Hickey, Eric A. Appel.
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