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Antibodies
Volume 15
Issue 1
10.3390/antib15010012
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Article

Comparative In Vitro Evaluation of Anti-HIV Immunotoxin, Antibody–Drug Conjugate, and Radioimmunoconjugate Targeted by the Same Antibody

by
Anne-Sophie Kuhlmann
1,*,
Tami Peters
2,
Donald K. Hamlin
3,
Yawen Li
3,
Xinyi Wang
1,
Megan Stackhouse
2,
Frances M. Cole
2,
Jasmin Martinez-Reyes
1,
Brenda M. Sandmaier
1,4,
Hans-Peter Kiem
1,4,
D. Scott Wilbur
3,
Robert D. Harrington
4 and
Seth H. Pincus
2,3,*
1
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA
2
Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA
3
Department of Radiation Oncology, School of Medicine, University of Washington, Seattle, WA 98195, USA
4
Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
*
Authors to whom correspondence should be addressed.
Antibodies 2026, 15(1), 12; https://doi.org/10.3390/antib15010012
Submission received: 25 November 2025 / Revised: 13 January 2026 / Accepted: 22 January 2026 / Published: 28 January 2026
(This article belongs to the Special Issue A Festschrift Celebrating Dr. Dimiter Stanchev Dimitrov: Antibodies, Innovation, and Impact on Infectious Disease and Cancer Research)
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Abstract

Background: We are developing cytotoxic immunoconjugates (CICs) to eliminate HIV-infected cells. We investigated the efficacy and kinetics of killing by different forms of CICs targeted by the same monoclonal antibody (mAb), an immunotoxin (IT), antibody-drug conjugate (ADC), and radioimmunoconjugate (RIC). Methods: We compared in vitro effects of CICs made by conjugating anti-gp41 mAb 7B2 to deglycosylated ricin A chain (7B2-dgA), the anthracycline derivative PNU-159682 (7B2-PNU), or the α-emitting isotope actinium-225 (7B2-225Ac). Kinetic analyses of cell growth were performed measuring electrical impedance every 15 min over a 7-day period using cells stably expressing the HIV envelope and Env-negative parent cells. Results: 7B2-dgA and 7B2-225Ac were more potent and acted more rapidly to kill cells than 7B2-PNU. Both the 7B2-PNU and 7B2-225Ac induced bystander-cell killing, whereas the IT did not and consequently allowed the outgrowth of Env-negative cells. Low dose or brief exposure to 7B2-PNU resulted in an increased rate of cell growth. Conclusions: An IT, ADC, and RIC showed substantial differences in the degree of specific toxicity, kinetics, and mechanisms of killing. The results of this side-by-side comparison have implications for the development of CICs to treat HIV, as well as other conditions.
Keywords: HIV reservoir eradication; monoclonal antibody; cytotoxic immunoconjugate; antibody-drug conjugate; immunotoxin; radioimmunoconjugate; immunotherapy; metabolomics; RNAseq; HIV envelope protein; gp160; gp41 HIV reservoir eradication; monoclonal antibody; cytotoxic immunoconjugate; antibody-drug conjugate; immunotoxin; radioimmunoconjugate; immunotherapy; metabolomics; RNAseq; HIV envelope protein; gp160; gp41

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MDPI and ACS Style

Kuhlmann, A.-S.; Peters, T.; Hamlin, D.K.; Li, Y.; Wang, X.; Stackhouse, M.; Cole, F.M.; Martinez-Reyes, J.; Sandmaier, B.M.; Kiem, H.-P.; et al. Comparative In Vitro Evaluation of Anti-HIV Immunotoxin, Antibody–Drug Conjugate, and Radioimmunoconjugate Targeted by the Same Antibody. Antibodies 2026, 15, 12. https://doi.org/10.3390/antib15010012

AMA Style

Kuhlmann A-S, Peters T, Hamlin DK, Li Y, Wang X, Stackhouse M, Cole FM, Martinez-Reyes J, Sandmaier BM, Kiem H-P, et al. Comparative In Vitro Evaluation of Anti-HIV Immunotoxin, Antibody–Drug Conjugate, and Radioimmunoconjugate Targeted by the Same Antibody. Antibodies. 2026; 15(1):12. https://doi.org/10.3390/antib15010012

Chicago/Turabian Style

Kuhlmann, Anne-Sophie, Tami Peters, Donald K. Hamlin, Yawen Li, Xinyi Wang, Megan Stackhouse, Frances M. Cole, Jasmin Martinez-Reyes, Brenda M. Sandmaier, Hans-Peter Kiem, and et al. 2026. "Comparative In Vitro Evaluation of Anti-HIV Immunotoxin, Antibody–Drug Conjugate, and Radioimmunoconjugate Targeted by the Same Antibody" Antibodies 15, no. 1: 12. https://doi.org/10.3390/antib15010012

APA Style

Kuhlmann, A.-S., Peters, T., Hamlin, D. K., Li, Y., Wang, X., Stackhouse, M., Cole, F. M., Martinez-Reyes, J., Sandmaier, B. M., Kiem, H.-P., Wilbur, D. S., Harrington, R. D., & Pincus, S. H. (2026). Comparative In Vitro Evaluation of Anti-HIV Immunotoxin, Antibody–Drug Conjugate, and Radioimmunoconjugate Targeted by the Same Antibody. Antibodies, 15(1), 12. https://doi.org/10.3390/antib15010012

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