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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 recognise and kill tumour cells.1

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

About KISIMA™ cancer vaccine (ATP-128)

The ATP-128 vaccine is based on the KISIMA® technology platform

Our ATP-128 cancer vaccine ATP-128 is a therapeutic chimaeric recombinant protein vaccine based on the KISIMA® technology platform.1 The KISIMA® platform is engineered to induce an efficient immune response via activation of helper and cytotoxic T cells, and to promote immunological memory.3

In order to induce a potent tumour-specific immune response, a therapeutic vaccine needs to stimulate multi-epitopic CD8+ cytotoxic T lymphocyte-mediated immunity, induce CD4+ helper T cells and promote immunological 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 tumours; 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 ATP-128 cancer vaccine is based on the KISIMA® technology platform, and includes three components designed to penetrate cells, raise a tumour-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.

Mechanism of action

Our KISIMA™ cancer vaccine (ATP-128) is designed to induce a tumour-specific adaptive immune response via the following hypothesised steps:1,3-5

  1. Administration: injection of the vaccine, which is taken up by antigen-presenting cells including dendritic cells
  2. Activation of the adaptive immune system: presentation of the CRC-specific multi-antigenic domain in draining lymph nodes results in stimulation of the adaptive immune system and activation of antigen-specific CD8+ and CD4+ T cells. Due to the self-adjuvanting nature of the KISIMA® platform, no additional adjuvant is required
  3. Anti-tumour activity of T cells and generation of immunological memory: cytotoxic T lymphocytes kill tumour cells and helper T cells promote the immunological memory necessary for a long-lasting anti-tumour immune response

Peptide-based immunotherapeutic cancer vaccine mechanism of action1,3-5

ATP-128 cancer vaccine mechanism of action

CD, cluster of differentiation; CRC, colorectal cancer; CTL, cytotoxic T lymphocyte; MHC, major histocompatibility complex.

Preclinical development

Preclinical evidence supports the safety and immunogenicity of a previous generation of the KISIMA™ cancer vaccine (ATP-128) 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 tumour 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

The vaccine also resulted in favourable changes in the tumour microenvironment, including tumour infiltration of antigen-specific effector T cells, reduction of myeloid-derived suppressor cells and regulatory T cells, and M1 polarisation 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, this could sensitise PD-1-resistant tumours (which have been shown to have limited immune infiltration) to checkpoint inhibitors.3

Clinical development

Our KISIMA™ cancer vaccine (ATP-128) is currently being investigated as a monotherapy and in combination with the PD-1 inhibitor BI 754091 in patients with Stage IV CRC.2

Colorectal cancer

Clinical trial of our KISIMA™ cancer vaccine (ATP-128) in patients with colorectal cancer

AE, adverse event; BOR, best overall response; DoR, duration of response; ORR, objective response rate; PD-1, programmed cell death protein 1; PFS, progression-free survival; RFS, relapse-free survival; RP2D, recommended Phase II dose.

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References

1

Boehringer Ingelheim. Press release. https://www.boehringer-ingelheim.com/press-release/acquisition-amal-therapeutics (Accessed: March 2020).

2

ClinicalTrials.gov. NCT04046445. https://clinicaltrials.gov/ct2/show/NCT04046445 (Accessed: March 2020).

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.

© 2020 Boehringer Ingelheim International GmbH. All rights reserved.

Page last updated: March 2020