What question did this study set out to answer?

The goal is to assess the efficacy of an anti-ALCAM ADC in treating hard-to-treat solid and hematologic malignancies.

April 5, 2026

Abstract 3167: Preclinical efficacy of a first-in-class anti-ALCAM ADC in hard-to-treat solid and hematologic malignancies

Key Points

The goal is to assess the efficacy of an anti-ALCAM ADC in treating hard-to-treat solid and hematologic malignancies.
Developed MAb52-29.1, an anti-ALCAM monoclonal antibody with selective binding to ALCAM.
Conjugated MAb52-29.1 with MMAE to create MAb52-29.1-ADC.
Evaluated antiproliferative effects in cancer cell lines and in vivo efficacy in xenograft mouse models.
Conducted preliminary toxicology studies on MAb52-29.1-ADC.
MAb52-29.1-ADC demonstrated strong cytotoxic effects with high internalization in cancer cells.
Complete tumor regression observed within 27 to 30 days after treatment in various xenograft models.
No safety concerns identified in initial toxicology assessments.

Abstract

Abstract ALCAM (CD166) is a type I transmembrane glycoprotein that mediates cell-cell adhesion through homophilic ALCAM-ALCAM and heterophilic ALCAM-CD6 interactions. ALCAM is aberrantly overexpressed across a variety of solid and hematologic malignancies. Using our proprietary live-cell immunization (LC-I) and high-throughput screening (LC-HTS) platforms, we developed MAb52-29.1, an anti-ALCAM monoclonal antibody that selectively recognizes a tumor-restricted conformational epitope of ALCAM, exhibiting minimal or no cross-reactivity with normal cells or tissues. Both the chimeric and humanized versions of MAb52-29.1 exhibited high binding affinities to recombinant ALCAM-ECD (KD ≈ 1.1 nM). MAb52-29.1 cAb, containing two point-mutations in each Fc, was conjugated to MMAE through an MC-Vc-PAB linker to produce MAb52-29.1-ADC (DAR4). MAb52-29.1-ADC demonstrated potent antiproliferative effects in vitro, with cytotoxicity correlating with its high antibody internalization efficiency in various cancer cell lines. Anti-tumor efficacy was demonstrated by a single intraperitoneal (i.p.) dose of MAb52-29.1-ADC at 4, 7, or 10 mg/kg using cell line-derived xenograft (CDX) mouse models of triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), gastric cancer (GC), and other tumor types, with subcutaneously inoculated tumors disappearing within 27∼30 days after treatment. Preliminary toxicology studies indicated that MAb52-29.1-ADC did not raise any safety concerns. These findings support MAb52-29.1-ADC as a promising therapeutic candidate for treating solid and hematologic malignancies, and potentially mitigating toxicity concerns. Ongoing studies aiming to support further clinical investigation include MAb52-29.1-ADC in patient-derived xenograft (PDX) gastrointestinal (GI) cancer models, along with retrospective analyses of its target expression in clinical tumor samples. Citation Format: Qinhong Ma, Daizong Li, Kewei Zhao, Mary Q. Xu, Mason Lu, . Preclinical efficacy of a first-in-class anti-ALCAM ADC in hard-to-treat solid and hematologic malignancies abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3167.

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