Potent <i>in vitro</i> and <i>in vivo</i> effects of polyclonal anti-human-myeloma globulins

Schieferdecker, Aneta; Shoshani, Ofer; Westner, Benedikt; Zipori, Dov; Ayuk, Francis

doi:10.18632/oncotarget.11489

Cited by 1 publication

(4 citation statements)

References 27 publications

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“…In conclusion, our study suggests, in agreement with other publications ( 15 – 20 , 35 , 61 ), that the therapeutic interest of pAb directed against tumor cells deserves to be revisited, now that engineered pAb with low immunogenicity become available ( 26 , 57 ). Our data lay the groundwork for further development of oncolytic pAb, which may hold the potential to improve the fate of patients with metastatic solid cancers.…”

Section: Discussionsupporting

confidence: 91%

“…However, this cannot be considered an absolute rule since, in another instance, an anti-4T1 rabbit pAb recognizes lung and brain tissues in IHC and presents an associated toxicity profile in vivo. The question whether heterologous pAb directed against tumor cell lines exhibit tissue specificity or not has not been addressed in earlier reports investigating their preclinical efficacy (15,18,20,35), and we still lack data to state whether target tumoral tissue specificity is the rule or the exception. Nevertheless, preclinical and clinical lessons from rabbit pAb raised against human T lymphocytes mostly show that target specificity can be achieved with animal-derived pAb.…”

Section: Discussionmentioning

confidence: 99%

“…Our data demonstrate that rabbit oncolytic pAb exhibit several mechanisms of action to kill tumor cells in vitro: CDC, apoptosis, and recruitment of effector cells for ADCC or ADCP through engagement of activating Fcγ receptors (FcR). Fc-mediated effector cell recruitment and functions such as ADCC or ADCP probably play crucial roles for tumor-targeting antibodies in various animal models -an observation already published (15,18,20,35). For example, the antibodies rituximab and trastuzumab lose their therapeutic activity in genetically modified mice that either lack expression of activating FcγR or are defective in FcγR signaling, while their efficacy is enhanced in FcγRIIb-KO mice (37,38).…”

Section: Gh-pab1 Gh-pab2 Gh-pab3mentioning

confidence: 99%

“…Targeting multiple tumor antigens with oncolytic pAb has demonstrated their efficacy initially in humans, more than a century ago, when Héricourt and Richet used sera from immunized animals to treat children with sarcomas (14). Then, multiple preclinical cancer models confirmed the oncolytic activity of pAb (15)(16)(17)(18)(19)(20). Their mechanism of action combines complement activation (complement-dependent cytotoxicity [CDC]) and cascade activation of effector T lymphocytes (21), recruitment of effector cells (antibody-dependent cellular cytotoxic [ADCC], antibody-dependent cellular phagocytosis [ADCP]), direct induction of apoptosis, and epitope masking, resulting in inhibition of molecular interactions.…”

Section: Introductionmentioning

confidence: 99%

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New polyclonal antibodies, inhibit selectively tumor growth and invasion and synergize with immune checkpoint inhibitors

Ciron,

Morice,

Rousse

et al. 2023

JCI Insight

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Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent preclinical models confirmed pAb efficacy, though their ability to tackle complex target antigens reduces susceptibility to tumor escape. Owing to the recent availability of glyco-humanized pAb (GH-pAb) with acceptable clinical toxicology profile, we revisited use of pAb in oncology and highlighted their therapeutic potential against multiple cancer types. Murine antitumor pAb were generated after repeated immunization of rabbits with murine tumor cell lines from hepatocarcinoma, melanoma, and colorectal cancers. Antitumor pAb recognized and showed cytotoxicity against their targets without cross-reactivity with healthy tissues. In vivo, pAb are effective alone; moreover, these pAb synergize with immune checkpoint inhibitors like anti–PD-L1 in several cancer models. They elicited an antitumor host immune response and prevented metastases. The anticancer activity of pAb was also confirmed in xenografted NMRI nude mice using GH-pAb produced by repeated immunization of pigs with human tumor cell lines. In conclusion, the availability of bioengineered GH-pAb allows for revisiting of passive immunotherapy with oncolytic pAb to fight against solid tumor and cancer metastasis.

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