ACB2112 – potentiating ICI therapy efficacy and eligibility for all colorectal cancer patients.

ACB2112 – potentiating ICI therapy efficacy and eligibility for all colorectal cancer patients

There exists a high unmet medical need for Colorectal Cancer (CRC) patients treated with Immune Checkpoint Inhibitors (ICI). Only 15% of patients have an MSI-H phenotype and are eligible for immunotherapy, with approximately 44%1 responding favorably to Keytruda™(anti-PD1). ICI therapy has failed to provide therapeutic benefit in the remaining 85% of CRC patients (MSS/MSI-L), leaving them without access to this life-saving therapy.


The key issue of non-responding CRC patients is immune escape by tumor cells by means of:


  • “pretending to be healthy” with low immunogenic tumor antigen (Ag) expression;
  • “hiding” by preventing immune recognition due to defects in TAP2-mediated, MHC-I-dependent antigen presentation
These tumors may also display:

  • immune suppression & exclusion” by immune checkpoint expression (e.g.: anti-PD1) and/or limited immune cell influx.

ACB2112 is effectively breaking immune escape

by means of:

  • Significantly reduces, in combination with anti-PD1, CRC tumor growth and improves tumor cell MHC-I expression cells in the resistant CT26 murine model.
  • Significantly increases expression of the TAP-complex components (TAP1 and TAP2) essential for MHC-I- dependent antigen presentation in CRC cell lines.

ACB2112 displays outstanding results in rendering anti-PD1 resistant mouse models susceptible to ICI therapy by targeting immune escape.

The clinical hypothesis is to render anti-PD1 therapy effective in 85% of non-responder patients (MSS/MSI-L) through a cotherapy with ACB2112.

  1. Merck & Co., Inc, Keytruda-Clinical Trial Results in Patients with Advanced MSI-H/dMMR Colorectal Cancer | Patients.
  2. Transporter associated with antigen processing (TAP) protein complex, comprised of TAP1 and TAP2, responsible for antigenic peptide loading onto Major histocompatibility complexes (MHC)-I containing Beta-2-microglobulin (B2m). Complexes are subsequently transported to the cell surface for antigen presentation to lymphocytes.