KISIMA™ cancer vaccine (ATP-128)

KISIMA cancer vaccine (ATP-128)

KISIMA™ cancer vaccine (ATP-128): a self-adjuvanting, multi-antigenic, peptide-based cancer vaccine

Our KISIMA™ cancer vaccine (ATP-128)* is a modular, self-adjuvanting peptide-based cancer vaccine that carries a multi-antigenic cargo, which has the potential to strengthen the capability of the patient’s immune system to recognize and kill tumor cells.1

Clinical trials (monotherapy and combination therapy): Our KISIMA™ cancer vaccine (ATP-128) is being investigated as a monotherapy and in combination with ezabenlimab* (BI 754091), a programmed death-1 (PD-1) inhibitor, in patients with advanced colorectal cancer (CRC).2 

About KISIMA™ cancer vaccine

This cancer vaccine is based on the KISIMATM​ technology platform

Our cancer vaccine is a therapeutic chimeric recombinant protein vaccine that is based on the KISIMATM technology platform.1 The KISIMATM platform is engineered to induce an efficient immune response via activation of helper and cytotoxic T cells, and to promote immunologic memory.3

In order to induce a potent tumor-specific immune response, a therapeutic vaccine needs to stimulate multi-epitopic CD8+ cytotoxic T lymphocyte-mediated immunity, induce CD4+ helper T cells and promote immunologic memory.4 Our KISIMA™ cancer vaccine (ATP-128) therefore includes three components in a single fusion protein, which is then used as a vaccine: first, a cell-penetrating peptide for antigen delivery; second, a multi-antigenic cargo that is tailored to raise an immune response against colorectal tumors; and third, a toll-like receptor (TLR) peptide agonist as an adjuvant.3

Functional components of our KISIMA™ cancer vaccine (ATP-128)3

Functional components of the ATP-128 vaccine
Our cancer vaccine is based on the KISIMATM technology platform, and includes three components that are designed to penetrate cells, raise a tumor-specific immune response and provide co-stimulatory signals.3 Adapted from Belnoue E, et al. JCI Insight 2019;4(11):e127305. TLR, toll-like receptor.

Watch the KISIMA™ cancer vaccine (ATP-128) mechanism of action animation

Watch the KISIMA™ cancer vaccine (ATP-128) mechanism of action animation

Mechanism of action

The KISIMA™ cancer vaccine (ATP-128) is engineered to induce an efficient immune response and promote immunologic memory via the activation of cytotoxic T cells and helper T cells.1,4,5

  1. The cell-penetrating peptide facilitates the delivery of the vaccine into antigen-presenting cells, such as dendritic cells
  2. The TLR component induces the upregulation of costimulatory molecules, activating dendritic cells
  3. Cancer-specific antigens are processed, and the presentation of the CRC-specific multi-antigenic domain activates antigen-specific CD8+ and CD4+ T cells
  4. CD8+ cytotoxic T cells become primed and educated to recognize and target tumor cells, while CD4+ helper T cells are triggered to release cytokines
  5. Cytokine release from T cells, as well as dendritic cells, leads to a cytotoxic T-cell response

 

Preclinical development

Preclinical evidence supports the safety and immunogenicity of a previous generation of the KISIMA™ cancer vaccine in an in vivo model of CRC.3 This cancer vaccine has been shown to induce highly potent helper and cytotoxic T-cell responses in several murine tumor models.3 The cell-penetrating peptide and the TLR agonist components of the vaccine platform have been shown to act together to elicit both CD8+ and CD4+ antigen-specific T-cell immune responses in vivo.3 

This previous generation of the cancer vaccine also resulted in favorable changes in the tumor microenvironment, including tumor infiltration of antigen-specific effector T cells, reduction of myeloid-derived suppressor cells and regulatory T cells, and M1 polarization of macrophages.3 

 

Combination therapy

Combination with PD-1 blockade has been shown to have an additive effect and to significantly increase the efficacy of the KISIMA™ cancer vaccine (ATP-128) in vivo.5 T-cell infiltration is enhanced, which could sensitize PD-1-resistant tumors (which have been shown to have limited immune infiltration) to checkpoint inhibitors.3

Peptide-based immunotherapeutic cancer vaccine mechanism of action1,4,5

KISIMA cancer vaccine (ATP-128) mechanism of action
CPP, cell-penetrating peptide; MAD, multiple antigenic domain; MHC, major histocompatibility complex; TCR, T-cell receptor; TLRag, toll-like receptor peptide agonist.

Clinical development

Our KISIMA™ cancer vaccine (ATP-128) is currently being investigated as a monotherapy and in combination with ezabenlimab (BI 754091) in patients with Stage IV CRC.2 

KISIMA™ cancer vaccine (ATP-128) clinical trial

CRC, colorectal cancer.
Trial number Phase Treatment Patient population Status

NCT040464452 (KISIMA-01)

Ib

KISIMA™ cancer vaccine (ATP-128) (monotherapy and in combination with ezabenlimab [BI 754091])

Histologically or cytologically confirmed Stage IV CRC

Recruiting

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References

1

Boehringer Ingelheim. Press release. https://www.boehringer-ingelheim.com/press-release/acquisition-amal-therapeutics (Accessed: February 2021).

2

ClinicalTrials.gov. NCT04046445. https://clinicaltrials.gov/ct2/show/NCT04046445 (Accessed: February 2021).

3

Belnoue E, et al. JCI Insight 2019;4(11):e127305.

4

AMAL Therapeutics. Therapeutic Vaccines. http://amaltherapeutics.com/science/therapeutic-vaccines/ (Accessed: March 2020).

5

Boehringer Ingelheim. Data on file.

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.

 

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Page last updated: March 2021