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MAb ID	CAP256V2LS
HXB2 Location	gp160	gp160 Epitope Map
Author Location	gp160
Epitope
Subtype	C
Ab Type	gp120 V2 // V2 glycan(V2g) // V2 apex
Neutralizing	P (tier2) View neutralization details
Species (Isotype)
Patient	CAP256
Immunogen	engineered
Keywords	binding affinity, broad neutralizer, immunotherapy, neutralization, structure

Notes

Showing 4 of 4 notes.

CAP256V2LS: The study examined protein forms created by tyrosine-O-sulfation of antibody CAP256V2LS. Previous reports had suggested that tyrosine-O-sulfation, a negative charged sulfo group (SO3-), of bNAbs may help establish a more robust intermolecular interaction between bNAbs and the antigen-binding site V1V2 domain of Env. CAP256V2LS was produced in CHO cells and fractionated based on sulfation. The fully sulfated (4-SO3) proteoform demonstrated the highest in vitro relative antigen binding potency and neutralization efficiency against a panel of HIV-1 viruses. Cai2022 (neutralization, binding affinity)
CAP256V2LS: A series of mutants was produced in the CAP256-VRC26.25 heavy chain, for the purpose of avoiding the previously-identified proteolytic cleavage at position K100m. Neutralization of the mutants was tested, and the cleavage-resistant variant that showed the greatest potency was K100mA. In addition to the K100mA mutation, an LS mutation was added to the Fc portion of the heavy chain, as this change has been shown to improve the half-life of antibodies used for passive administration without affecting neutralization potency. The resulting construct was named CAP256V2LS. The pharmacokinetics of CAP256V2LS were assessed in macaques and mice, and it showed a profile similar to other antibodies used for immunotherapy. The antibody lacked autoreactivity. Structural analysis of wild-type CAP256-VRC26.25 showed that the K100m residue is not involved in interaction with the Env trimer. Zhang2022 (neutralization, immunotherapy, broad neutralizer)
CAP256V2LS: This study used LC-MS to define the glycosylation, disulfide bonding, and other post-transcriptional modifications of CAP256-VRC26.25-LS. The mAb was found to be susceptible to clipping in the CDRH3 region, at the L117-Q118 site. Ivleva2018 (structure)
CAP256V2LS: This study describes the design of the CAPRISA 012B human trial to assess the safety and pharmacokinetics of CAP256V2LS. Escalating dosages of CAP256V2LS, alone and in combination with 2 other mAbs (VRC07-523LS, PGT121) will be given to 52 HIV-negative and 14 HIV-positive women. Results will be reported in a future study. Mahomed2020 (immunotherapy)

References

Showing 4 of 4 references.

Isolation Paper
Zhang2022 and Baoshan Zhang. Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life, , :, 2022. Show all entries for this paper.

Cai2022 Cindy X. Cai, Nicole A. Doria-Rose, Nicole A. Schneck, Vera B. Ivleva, Brad Tippett, William R. Shadrick, Sarah O'Connell, Jonathan W. Cooper, Zachary Schneiderman, Baoshan Zhang, Daniel B. Gowetski, Daniel Blackstock, Jacob Demirji, Bob C. Lin, Jason Gorman, Tracy Liu, Yile Li, Adrian B. McDermott, Peter D. Kwong, Kevin Carlton, Jason G. Gall, and Q. Paula Lei. Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency. Sci Rep, 12(1):8433 doi, May 2022. PubMed ID: 35589938 Show all entries for this paper.

Ivleva2018 Vera B. Ivleva, Nicole A. Schneck, Deepika Gollapudi, Frank Arnold, Jonathan W. Cooper, and Q. Paula Lei. Investigation of Sequence Clipping and Structural Heterogeneity of an HIV Broadly Neutralizing Antibody by a Comprehensive LC-MS Analysis. J Am Soc Mass Spectrom, 29(7):1512-1523 doi, Jul 2018. PubMed ID: 29736600 Show all entries for this paper.

Mahomed2020 Sharana Mahomed, Nigel Garrett, Quarraisha A. Karim, Nonhlanhla Y. Zuma, Edmund Capparelli, Cheryl Baxter, Tanuja Gengiah, Derseree Archary, Natasha Samsunder, Nicole D. Rose, Penny Moore, Carolyn Williamson, Dan H. Barouch, Patricia E. Fast, Bruno Pozzetto, Catherine Hankins, Kevin Carlton, Julie Ledgerwood, Lynn Morris, John Mascola, and Salim Abdool Karim. Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial. BMJ Open, 10(11):e042247 doi, Nov 2020. PubMed ID: 33243815 Show all entries for this paper.