Pre-existing antitherapeutic antibodies against the Fc region of the hu14.18K322A mAb are associated with outcome in patients with relapsed neuroblastoma
| Autor: | Michael M Meager, Fenna de Bie, Jacqueline A Hank, Michael W. Bishop, KyungMann Kim, Steven D. Gillies, Jacob L Goldberg, Amy K. Erbe, Michael Merdler, Janardan P. Pandey, Amal M. Javaid, Lakeesha Carmichael, Jacek Gan, Victor M. Santana, Paul M. Sondel, Anna Hoefges, Fariba Navid |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.drug_class medicine.medical_treatment Immunology Short Report Monoclonal antibody pre-existing antitherapeutic antibodies (PATA) 03 medical and health sciences neuroblastoma 0302 clinical medicine rituximab human antihuman antibody (HAHA) medicine Immunology and Allergy Panitumumab RC254-282 Pharmacology mAb biology business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Dinutuximab Immunotherapy anti-GD2 Fragment crystallizable region Isotype 3. Good health 030104 developmental biology Oncology pre-existing antibodies 030220 oncology & carcinogenesis hu14.18K322A biology.protein Molecular Medicine Rituximab immunotherapy Antibody business medicine.drug |
| Zdroj: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020) |
| ISSN: | 2051-1426 0074-3496 |
| Popis: | PurposePatients with cancer receiving tumor-reactive humanized monoclonal antibody (mAb) therapy can develop a human antihuman antibody (HAHA) response against the therapeutic mAb. We evaluated for HAHA in patients with neuroblastoma treated in a phase I study of humanized anti-GD2 mAb (immunoglobulin (Ig)G1 isotype), hu14.18K322A (NCT00743496). The pretreatment sera (collected prior to mAb treatment) from 9 of 38 patients contained antitherapeutic antibodies, even though they had no prior mAb exposure. We sought to characterize these pre-existing antitherapeutic antibodies (PATA).Experimental designThe PATA+ pretreatment samples were characterized via ELISA; clinical associations with PATA status were evaluated.ResultsPretreatment sera from eight of nine PATA+ patients also bound rituximab and demonstrated preferential ELISA reactivity against the Fc portions of hu14.18K322A and rituximab as compared with the Fab portions of these mAbs. These PATA+ sera also recognized dinutuximab (human IgG1 isotype) and mouse IgG2a isotype mAbs, but not a mouse IgG1 isotype or the fully human panitumumab (IgG2 isotype) mAb. Of the 38 treated patients, only 4 patients (all in the PATA+ cohort) demonstrated no disease progression for>2.5 years without receiving further therapy (p=0.002).ConclusionsThis study demonstrates an association between clinical outcome and the presence of PATA against determinant(s) on the Fc component of the therapeutic mAb, suggesting that the PATA may be playing a role in augmenting mAb-based antitumor effects. Further analyses for the presence of PATA in a larger cohort of patients with relapsed neuroblastoma, analyses of their clinical correlates, identification of their immunological targets, and potential antitumor mechanisms are warranted. |
| Databáze: | OpenAIRE |
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