Molecule

This compound is designed to be a modular, self-adjuvanting, peptide-based cancer vaccine that has the potential to strengthen the capability of the patient’s immune system to recognize and kill tumor cells.^1–3 Designed using the KISIMA^TM technology platform, the investigational vaccine includes three components^1–3 :

• A cell-penetrating peptide for antigen delivery

• A multi-antigenic cargo that is tailored to raise an immune response against colorectal tumors 

• A TLR peptide agonist as an adjuvant

Proposed MoA

The investigational vaccine is engineered to induce an efficient immune response and promote immunological memory via activation of cytotoxic T cells and helper T cells.^1–3

The cell penetrating peptide facilitates delivery of the investigational vaccine into dendritic cells. The TLR component may induce the upregulation of costimulatory molecules activating dendritic cells. Cancer-specific antigens are processed and resulting epitopes presented to T cells. Cytotoxic T cells become primed and educated to recognize and target tumor cells, and helper T cells become primed, triggering the release of cytokines. Cytokine release from T cells, as well as dendritic cells, leads to a cytotoxic T-cell response.

Proposed MoA¹

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Combination therapy rationale

Preclinical evidence supports the immunogenicity of a previous generation of the cancer vaccine in an in vivo model of CRC.⁴ This may lead to immunological memory and high vaccine efficacy, with increased intratumoral leukocyte infiltration.⁴ 

Combination with PD-1 blockade has been shown to have an additive effect, and may significantly increase the efficacy of the vaccine in vivo.¹ As the vaccine enhances T-cell infiltration, this could sensitize tumors that are resistant to PD-1 inhibition (some of which have been shown to have limited immune infiltration) to checkpoint inhibitors.^1,4

Note: this information reflects KISIMA-1. Patients are now being enrolled into KISIMA-2.