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oai:ubir.buffalo.edu:10477/840942025-07-16T19:39:47Zcom_10477_77914col_10477_81567

Investigating the Pharmacokinetics and Pharmacodynamics of Antibody-Drug Conjugates, T Cells and Bispecific Antibodies Khot, Antari; 0000-0002-2388-5046 Shah, Dhaval Pharmaceutical Sciences pharmaceutical sciences Ph.D. Antibody-based therapeutics have been in development for treating cancer by increasing specificity and decreasing off-target toxicity. Many therapies, such as antibody-drug conjugates (ADCs), immune cells redirecting bispecific antibodies, and engineered T cells, take advantage of the targeting properties of antibodies to deliver cytotoxic drugs or to harness the power of immune system against cancer. This dissertation focuses on understanding the pharmacokinetics and pharmacodynamics of such therapies. ADCs have small molecule drugs attached to an antibody via chemical or peptide linkers. The idea behind the development of ADCs is that antibodies can be used to target fast internalizing surface receptors in cancer cells and deliver DNA damaging or anti-mitotic agents that lead to cell death. Pharmacokinetics of ADCs is complicated due to the generation of multiple pharmacologically active species in a biological system such as antibody with a different number of payloads attached, shed payload, and naked antibody. All of these species can have different pharmacokinetic behavior due to their size and physicochemical properties. **To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.** 2022-06-21T15:47:52Z 2022-06-21T15:47:52Z 2020 Text Dissertation http://hdl.handle.net/10477/84094 eng Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions. Copyright retained by author. application/pdf State University of New York at Buffalo