CBR96-doxorubicin immunoconjugate

CBR96-doxorubicin immunoconjugate
Monoclonal antibody
Type	?
Source	Humanized (from mouse)
Target	Lewis-Y antigen
Clinical data
Other names	SGN-15, BMS-182248
ATC code	none
Identifiers
CAS Number	160612-45-3
ChemSpider	none

cBR96-doxorubicin immunoconjugate (BMS-182248/SGN-15; also known as cBR96-Dox) is an antibody-drug conjugate or (ADC) directed to the Lewis-Y antigen designed for the treatment of cancer. The payload is the chemotherapy drug doxorubicin which is connected with a hydrazone linker to cysteine residues of the Lewis-Y specific (chimeric) monoclonal antibody BR96.^[1] Following internalization, the hydrazone is hydrolyzed within the acidic environment of target cell endosomes and lysosomes to release active cytotoxic drug.

Clinical Development

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In clinical trials cBR96-Dox was found to be highly active in regressing large human tumor xenografts implanted in mice or rats.^[2]^[3] Multiple tumor models including lung, breast and colon were evaluated, and cBR96-Dox was found to have broad and potent anti-tumor activity, even in doxorubicin-resistant tumors.

References

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^ Hofland P (2013). "Harnessing The Power of Three: Advancing Antibody-drug Conjugates from Laboratory to Bedside". ADC Review / Journal of Antibody-drug Conjugates. 1. doi:10.14229/jadc.2013.6.1.001.
^ Trail PA, Willner D, Lasch SJ, Henderson AJ, Hofstead S, Casazza AM, Firestone RA, Hellström I, Hellström KE (July 1993). "Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates". Science. 261 (5118): 212–5. Bibcode:1993Sci...261..212T. doi:10.1126/science.8327892. PMID 8327892.
^ Sjögren HO, Isaksson M, Willner D, Hellström I, Hellström KE, Trail PA (October 1997). "Antitumor activity of carcinoma-reactive BR96-doxorubicin conjugate against human carcinomas in athymic mice and rats and syngeneic rat carcinomas in immunocompetent rats". Cancer Research. 57 (20): 4530–6. PMID 9377565.

Monoclonal antibodies for tumors

Tumor

Human	Adecatumumab^§ Amivantamab Ascrinvacumab^§ Atezolizumab (+hyaluronidase) Balstilimab^† Botensilimab Cixutumumab^§ Conatumumab^§ Daratumumab Drozitumab^§ Duligotumab^§ Dusigitumab^§ Enfortumab vedotin Enoticumab^§ Figitumumab^§ Flanvotumab^§ Ganitumab^† Glembatumumab vedotin^† Intetumumab^§ Ipilimumab Iratumumab^§ Istiratumab Icrucumab^§ Lexatumumab^§ Lucatumumab^§ Mapatumumab^§ Narnatumab^§ Necitumumab Nesvacumab^§ Nivolumab^# Ofatumumab Olaratumab^† Panitumumab Patritumab^§ Pembrolizumab^# Pritumumab^§ Radretumab^§ Ramucirumab Rilotumumab^† Robatumumab^§ Seribantumab^§ Sugemalimab Tarextumab^§ Tisotumab vedotin Teprotumumab^† Tovetumab^§ Vantictumab^§ Votumumab^§ Zalutumumab^†
Mouse	Abagovomab Altumomab pentetate Anatumomab mafenatox Arcitumomab Bectumomab Blinatumomab Capromab pendetide Detumomab Edrecolomab Ibritumomab tiuxetan Igovomab Lilotomab Minretumomab Mitumomab Nacolomab tafenatox Moxetumomab pasudotox Naptumomab estafenatox Oregovomab Pemtumomab^† Racotumomab Satumomab pendetide Solitomab Taplitumomab paptox Nofetumomab merpentan Pintumomab Tenatumomab Tositumomab
Chimeric	Amatuximab^§ Bavituximab^§ Brentuximab vedotin Carotuximab^† Cetuximab Derlotuximab biotin^§ Dinutuximab Ecromeximab^§ Ensituximab^§ Futuximab^§ Girentuximab^† Indatuximab ravtansine^§ Isatuximab Loncastuximab tesirine Margetuximab Mirvetuximab soravtansine Rituximab^# Siltuximab Ublituximab Zolbetuximab
Humanized	Abituzumab^§ Alemtuzumab Axatilimab Belantamab mafodotin Bevacizumab Bivatuzumab mertansine^§ Brontictuzumab^§ Cantuzumab mertansine^§ Cantuzumab ravtansine^§ Cirmtuzumab Citatuzumab bogatox^§ Clivatuzumab tetraxetan Cofetuzumab pelidotin Dacetuzumab^§ Demcizumab^§ Dalotuzumab^§ Denintuzumab mafodotin^§ Elotuzumab Emactuzumab Emibetuzumab^§ Enoblituzumab^§ Epcoritamab Etaracizumab^§ Farletuzumab^§ Ficlatuzumab^§ Flotetuzumab^§ Gemtuzumab ozogamicin Glofitamab Imgatuzumab^§ Inotuzumab ozogamicin Labetuzumab^§ Lifastuzumab vedotin^§ Lintuzumab^§ Lorvotuzumab mertansine^§ Lumretuzumab^§ Matuzumab^§ Milatuzumab^§ Naxitamab Nimotuzumab^† Obinutuzumab Ocaratuzumab^§ Odronextamab Otlertuzumab^§ Onartuzumab^§ Oportuzumab monatox^† Parsatuzumab^§ Pertuzumab Pinatuzumab vedotin^§ Polatuzumab vedotin Rosmantuzumab Rovalpituzumab tesirine^† Sacituzumab govitecan Sibrotuzumab^§ Simtuzumab^§ Sofituzumab vedotin^§ Tacatuzumab tetraxetan^§ Tigatuzumab^§ Trastuzumab^# (+deruxtecan / +emtansine) Tucotuzumab celmoleukin^§ Vandortuzumab vedotin^§ Vanucizumab^§ Veltuzumab^§ Vorsetuzumab mafodotin^§
Rat/mouse hybrid	Catumaxomab Ertumaxomab^§
Chimeric + humanized	Depatuxizumab mafodotin^† Duvortuxizumab Ontuxizumab^§

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III