VB10.NEO and NKTR-214 Work Together to Drive Complete, Durable Tumor Regression, Study Says

Vaccibody‘s VB10.NEO and Nektar Therapeutics‘ bempegaldesleukin (NKTR-214 or bempeg) work together to trigger a strong immune response against cancer cells, resulting in complete and durable tumor regression in a mouse model of colon cancer, a recent study says.

The findings were featured in the poster, “Combination of neoantigen DNA plasmid vaccine VB10.NEO and NKTR-214, a CD122-biased immunostimulatory cytokine, induces strong neoantigen-specific T cell responses and sustained tumor regression in pre-clinical models,” presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, in Atlanta, Georgia.

VB10.NEO is an investigational cancer vaccine that targets specific antigens (substances seen as threats by the immune system) on the surface of cancer cells, called neoantigens. These unique antigens arise from genetic mutations that gradually accumulate and turn normal healthy cells into malignant cancer cells. The vaccine is intended for patients with locally advanced or metastatic solid tumors.

NKTR-214 is a type of immunotherapy that works by stimulating the expansion of T-cells that are able to recognize and eliminate cancer cells. The combined therapy of VB10.NEO and NKTR-214 is designed to generate a massive number of T-cells instructed to recognize neoantigens on the surface of cancer cells to attack and destroy the tumor.

“We are excited to present these novel preclinical data that show combining bempeg with VB10.NEO synergize to increase both the breadth and the depth of the neoantigen-specific immune response. These unique and non-overlapping mechanisms produced an expansion of the VB10.NEO elicited neoantigen-specific T cells and demonstrated enhanced anti-tumor efficacy in mice,” Agnete B. Fredriksen, PhD, Vaccibody’s president and chief scientific officer, said in a press release.

According to the findings presented at the AACR meeting, animals that had been treated with VB10.NEO and NKTR-214 were able to mount an immune response against neoantigens that was nearly five-fold higher compared to mice treated with VB10.NEO alone.

Although the combination therapy triggered a strong immune response in both CD4-positive and CD8-positive T-cells, this effect was more pronounced on CD8-positive T-cells (cells with tumor-killing abilities), whose activity was six times higher compared to mice treated with VB10.NEO only.

Mice with colon cancer treated with a triple combination of VB10.NEO, NKTR-214, and anti-PD-1 therapy achieved a complete and durable tumor regression, supporting the rationale for testing this new combination therapy in human subjects. Of note, anti-PD-1 immune checkpoint inhibitors block the binding of the PD-L1 protein from tumor cells to the PD-1 receptor on immune cells, preventing the cancer from shutting down the immune system.

“Personalized T cell vaccines could play a critical and central role in cancer immunotherapy,” said Jonathan Zalevsky, PhD, chief scientific officer at Nektar. “These preclinical data highlight the potential of combining a personalized cancer vaccine with a T cell proliferator to induce maximal expansion of vaccine-induced T cell clones and durable responses and specific anti-tumor immunity.

“We are highly encouraged by these results and look forward to testing this unique approach to personalized cancer treatment in patients with squamous cell carcinoma of the head and neck,” Zalevsky added. 

Last year Vaccibody and Nektar entered into a collaboration agreement to test the therapeutic potential of the combination therapy of VB10.NEO and NKTR-214. The companies are now planning to launch a pilot Phase 1 clinical trial to assess the safety and effectiveness of the treatment in patients with squamous cell carcinoma of the head and neck by mid-2019.