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Antibody-dependent cellular phagocytosis of tropomyosin receptor kinase C (TrkC) expressing cancer cells for targeted immunotherapy

Lai PS 1 , Usama SM 2 , Kiew LV 3 , Lee HB 4 , Chung LY 5 , Burgess K 6 Show all authors , Kue CS 7

Affiliations 

  • 1 School of Graduates Studies, Management and Science University, Seksyen 13, 40100, Shah Alam, Selangor, Malaysia
  • 2 Department of Chemistry, Texas A & M University, Box 30012, College Station, TX, 77842, USA
  • 3 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
  • 4 School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia
  • 5 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Malaya, 50603, Kuala Lumpur, Malaysia
  • 6 Department of Chemistry, Texas A & M University, Box 30012, College Station, TX, 77842, USA. burgess@chem.tamu.edu
  • 7 Faculty of Health and Life Sciences, Management and Science University, Seksyen 13, 40100, Shah Alam, Selangor, Malaysia. cskue@msu.edu.my
Cancer Immunol Immunother, 2022 Sep;71(9):2099-2108.
PMID: 35032175 DOI: 10.1007/s00262-022-03147-y

Abstract

Conventional cancer therapies such as chemotherapy are non-selective and induce immune system anergy, which lead to serious side effects and tumor relapse. It is a challenge to prime the body's immune system in the cancer-bearing subject to produce cancer antigen-targeting antibodies, as most tumor-associated antigens are expressed abundantly in cancer cells and some of normal cells. This study illustrates how hapten-based pre-immunization (for anti-hapten antibodies production) combined with cancer receptor labeling with hapten antigen constructs can elicit antibody-dependent cellular phagocytosis (ADCP). Thus, the hapten antigen 2,4-dinitrophenol (DNP) was covalently combined with a cancer receptor-binding dipeptide (IYIY) to form a dipeptide-hapten construct (IYIY-DNP, MW = 1322.33) that targets the tropomyosin receptor kinase C (TrkC)-expressed on the surface of metastatic cancer cells. IYIY-DNP facilitated selective association of RAW264.7 macrophages to the TrkC expressing 4T1 cancer cells in vitro, forming cell aggregates in the presence of anti-DNP antibodies, suggesting initiation of anti-DNP antibody-dependent cancer cell recognition of macrophages by the IYIY-DNP. In in vivo, IYIY-DNP at 10 mg/kg suppressed growth of 4T1 tumors in DNP-immunized BALB/c mice by 45% (p 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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