Polyclonal antibodies selectively inhibit tumor growth and invasion and synergize with immune checkpoint inhibitors

Area of Science:

• Oncology
• Immunotherapy
• Biotechnology

Background:

• Polyclonal antibodies (pAb) have a long history of oncolytic properties, with early clinical responses noted.
• Preclinical models confirm pAb efficacy, but challenges with complex tumor antigens can lead to tumor escape.
• Recent advancements in glyco-humanized pAb (GH-pAb) offer an improved safety profile for clinical use.

Purpose of the Study:

• To re-evaluate the therapeutic potential of oncolytic polyclonal antibodies (pAb) in cancer treatment.
• To investigate the efficacy of glyco-humanized pAb (GH-pAb) against multiple cancer types.
• To explore the synergistic effects of pAb with immune checkpoint inhibitors.

Main Methods:

• Generation of murine antitumor pAb via immunization of rabbits with specific murine tumor cell lines (hepatocarcinoma, melanoma, colorectal).
• In vitro assessment of pAb cytotoxicity against target cancer cells and evaluation of cross-reactivity with healthy tissues.
• In vivo studies using pAb alone and in combination with anti-PD-L1 in various cancer models, including xenograft models with GH-pAb in NMRI nude mice.

Main Results:

• Antitumor pAb demonstrated specific recognition and cytotoxicity against target cancer cells without affecting healthy tissues.
• In vivo, pAb exhibited monotherapy efficacy, synergized with anti-PD-L1, elicited host immune responses, and prevented metastasis.
• GH-pAb also confirmed anticancer activity in xenograft models, validating their therapeutic potential.

Conclusions:

• Bioengineered GH-pAb represent a significant advancement in passive immunotherapy for cancer.
• Oncolytic pAb hold promise for treating solid tumors and combating cancer metastasis.
• The combination of pAb with immunotherapies like checkpoint inhibitors offers a potent strategy against diverse cancers.