Adaptimmune and Noile-Immune Forge $312M Collaboration to Develop Next-Generation SPEAR T-Cell Therapy Co-Expressing IL-7 and CCL19

Today, Adaptimmune Therapeutics, a developer of T-cell cancer therapies, announced a collaborative development agreement with Noile-Immune Biotech Inc., a Japanese biotechnology company focused on innovative cancer immunotherapies. The two companies will join forces to develop next-generation T-cell products that combine Adaptimmune’s SPEAR T (Specific Peptide Enhanced Affinity Receptor) cell technology with Noile-Immune’s PRIME (Proliferation inducing and migration enhancing) technology. The new generation of SPEAR T-cell products will co-express the chemokines IL-7 and CCL19. PRIME technology has already been utilized to enhance the efficacy of CAR-T cell therapies.

Under the terms of the agreement, Adaptimmune will hold exclusive global rights for the development and commercialization of the final products. Noile-Immune will receive upfront and milestone payments totaling up to $312 million, as well as royalties on future sales. The two companies plan to obtain regulatory approval for the first product to enter human clinical trials by 2021.

Adaptimmune’s SPEAR T-cells are a type of TCR-T cell therapy. TCR (T-cell receptor) is a receptor on the surface of T cells that specifically recognizes antigens and mediates immune responses. Adaptimmune’s proprietary recognition system identifies antigen peptides presented by HLA molecules that are specific to cancer cells. It then uses genetic engineering technology to modify the variable region of the T-cell receptor, enabling it to specifically recognize the aforementioned peptides. This enhances the sensitivity of T cells in recognizing cancer cells and strengthens their ability to destroy cancer cells. Currently, ADAP has three SPEAR T-cell products under development (targeting MAGE-A4, MAGE-A10, and AFP), aimed at treating various solid tumor indications.

▲Adaptimmune’s Engineered T Cell Therapy (Image source: Adaptimmune official website)

Noile-Immune’s PRIME technology utilizes genetic engineering to modify T cells, enabling them to express cytokines and chemokines (such as IL-7 and CCL19), thereby enhancing T cell expansion, accumulation, and the induction of memory functions, making them suitable for the treatment of solid tumors.

Previous studies have shown that reticular fibroblasts in lymphoid tissues can secrete the chemokine IL-7 and CCL19, where CCL19 recruits peripheral T cells and dendritic cells into lymphoid tissues, while IL-7 promotes T cell proliferation and maintains T cell stability.

On March 5, 2018, Nature Biotechnology published online a landmark study demonstrating that next-generation CAR-T cells co-expressing IL-7 and CCL19 exhibited twice the proliferative capacity of conventional CAR-T cells. These engineered cells effectively induced substantial infiltration of endogenous T cells and dendritic cells into the tumor microenvironment of solid tumors, thereby enhancing tumor cell killing. While conventional CAR-T therapy is largely ineffective against lung adenocarcinoma and pancreatic cancer, CAR-T cells co-expressing IL-7 and CCL19 achieved complete tumor eradication in mouse models of lung adenocarcinoma and sustained long-term tumor suppression in pancreatic cancer models, significantly prolonging survival. This study highlights the potential of IL-7 and CCL19 co-expressing CAR-T therapy for the treatment of solid tumors.

▲ In the CAR-T therapy group co-expressing IL-7 and CCL19, 100% of mice with murine mast cell tumor survived (red line), whereas the survival rate in the conventional CAR-T therapy group was only approximately 30% (blue line) (Image source: Reference [2])

Note: The original text has been abridged.

References:

[1]. Adaptimmune and Noile-Immune Announce Agreement to Develop SPEAR T-Cell Products expressing IL-7 and CCL19 as a next-generation treatment for cancer patients. Retrieved Aug. 27, 2019, from https://finance.yahoo.com/news/adaptimmune-noile-immune-announce-agreement-120000147.html

[2]. Tamada. et al. （2018）IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nature biotechnology. https://www.nature.com/articles/nbt.4086#auth-6

Flash | $300 Million Collaboration to Develop “Next-Generation” T-Cell Therapy

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