Research Lab Overview

“My research rationale and curiosity have always been driven by the immense promise of antibodies for cancer therapy, and especially by efforts to improve, personalize and expand our understanding of targeted therapies.”

Our laboratory focuses on the development of antibody fragments with pharmacokinetics optimized for imaging or therapy. We use antibody engineering techniques to modulate the molecular size, valency, effector functions and half-life of antibodies specific for tumor-associated antigens or immune cell markers.

The engineered antibody fragments are then used to deliver payloads to the target cells or tissues. These payloads can be radionuclides for positron emission tomography (PET) imaging, fluorescent molecules for optical imaging or radionuclides that deliver cytotoxic radiation (alpha- or beta-emitters) for radioimmunotherapy. The high specificity of antibodies for their antigen results in accumulation of signal at the target site and lowers non-specific uptake in healthy tissues.

We evaluate our antibody fragment-based theranostics in preclinical models of prostate, pancreatic or breast cancer in wild-type, immunodeficient, antigen knock-in or transgenic mice.

Research Highlights

We are currently working on the following projects:

Development of anti-CD20 antibody fragments for immunoPET imaging of tumor-infiltrating B cells in breast cancer.
New half-life modulated anti-PSCA antibody fragments with optimized pharmacokinetics for radioimmunotherapy of prostate and pancreatic cancer.
Near-infrared dye conjugated anti-PSCA antibody fragments for real-time surgical guidance by fluorescent imaging during cancer resection.
Re-engineered anti-PSCA cys-diabody as companion diagnostic for targeted PSCA therapies.

Principal Investigator: Kirstin Anja Zettlitz, Ph.D.

Kirstin Anja Zettlitz, Ph.D., is assistant professor in the Department of Immunology & Theranostics, Arthur-Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope.

Dr. Zettlitz’s research interest focuses on the use of antibody-based molecular imaging to guide and improve the development and clinical translation of targeted therapies.

Full bio

Lab Members

Masoud Farshbaf, Ph.D., M.Sc.

Postdoctoral Fellow

The research interests of Masoud Farshbaf, Ph.D., M.Sc., focus on the application of engineered antibodies and antibody fragments for imaging and therapy of cancer. These applications include optical and PET imaging, as well as radioimmunotherapy and image-guided surgery. He is developing an anti-prostate stem cell antigen (PSCA) antibody fragment for near-infrared fluorescence imaging for real-time surgical guidance, for example during prostate cancer resection and uses immunoPET imaging to profile the in vivo targeting, biodistribution and pharmacokinetics of the novel tracers. Dr. Farshbaf received his B.Sc. degree in biomedical engineering (bioelectric) from Sahand University of Technology, Tabriz, Iran in 2014. He received his M.Sc. (2017) and Ph.D. (2022) in Medical Nanotechnology from Tabriz University of Medical Sciences, Tabriz, Iran. As his Ph.D. thesis, he investigated the capability of peptide-decorated lipid nanoparticles for targeted drug delivery to brain cancer cells. His main interests include active targeting, drug delivery, advanced imaging systems, protein corona, and translational medicine.

Ujwala R Vedavally, B.V.Sc. & A.H., MPVM

Research Associate II

Ujwala received her Master’s degree in Preventive Veterinary Medicine (MPVM) from the University of California Davis in 2023 and her Bachelor’s degree in Veterinary Science and Animal Husbandry (B.V.Sc. & A.H.) from P.V. Narasimha Rao Telangana Veterinary University, India in 2020.Ujwala’s research in the Zettlitz lab focuses on the engineering of novel antibody fragments for molecular imaging and targeted therapies. This involves the production, purification, and conjugation of the antibody fragments, as well as their evaluation for immunoPET imaging in preclinical mouse models of cancer.In her leisure time, she likes playing table tennis and making crafts.

Christi Turner, Ph.D.

Postdoctoral Fellow

My research is focused on investigating CD20 B cells and tertiary lymphoid structures using antibody engineering and immunoPET. Anti-CD20 immunoPET helps us to visualize the B cell repertoire systemically and within tumors. B cells are a positive prognostic biomarker in multiple cancers and this antibody targeting approach may help to identify non-responders versus responders of immunotherapy leading to greater treatment outcomes for patients. Fun fact: I truly enjoy the outdoors and am an avid “fisherwoman."Ph.D. in Quantitative Systems and Biology, University of California Merced 2023 M.S. in Biomedical Science, Western University of Health Sciences 2016B.S. in Biology, Oral Roberts University 2009

News

Conference Contributions:

RSO Advance 2024, Apr 28-30, 2024, Lake Arrowhead, CA. Masoud Farshbaf et. al., Near-Infrared Fluorescent Anti-PSCA Antibody Fragments Improve the Intraoperative Prostate Cancer Visualization. Poster Award.
GRC Radionuclide Theranostics for the Management of Cancer, July 7-12, 2024, Newry, Maine. Kirstin Zettlitz et. al., Optimizing radioimmunotherapy for prostate cancer: Evaluating novel pharmacokinetics-modulated anti-prostate stem cell antigen (PSCA) antibody fragments using 89Zr-immunoPET.
WMIC 2024, Sept. 9-13, 2024, Montreal, Canada. Masoud Farshbaf et. al., A near-infrared fluorophore-conjugated antibody fragment (A2DM) specific for prostate stem cell antigen (PSCA) yields high-contrast fluorescent images in a human PSCA knock-in syngeneic model.

Alumni

Saad N Ahmed, B.Sc., Research Associate I. Current: Medical Student, University of Chicago Pritzker School of Medicine.
Sunidhi Jaiswal, Ph.D., Postdoctoral Fellow. Current: Postdoctoral Researcher, University of California San Diego

Previous students

2023, Marc Herman (AR-DMRI Summer Research Program)
2023, Tamer Siam (Eugene and Ruth Roberts Summer Academy)
2022, Lara Avsharian (Irell and Manella Graduate School of Biological Sciences; graduate rotation)

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Publications

Chan AM, Olafsen T, Tsui J, Salazar FB, Aguirre B, Zettlitz KA, Condro M, Wu AM, Braun J, Gordon LK, Ashki N, Whitelegge J, Xu S, Ikotun O, Lee JT, Wadehra M. 89Zr-ImmunoPET for the Specific Detection of EMP2-Positive Tumors. Mol Cancer Ther. 2024 Feb 28;. doi: 10.1158/1535-7163.MCT-23-0465. [Epub ahead of print] PubMed PMID: 38417138.

Zettlitz KA, Salazar FB, Yamada RE, Trinh KR, Vasuthasawat A, Timmerman JM, Morrison SL, Wu AM. 89Zr-ImmunoPET Shows Therapeutic Efficacy of Anti-CD20-IFNα Fusion Protein in a Murine B-cell Lymphoma Model. Mol Cancer Ther. 2022 Apr 1;21(4):607-615. doi: 10.1158/1535-7163.MCT-21-0732. PubMed PMID: 35086952; PubMed Central PMCID: PMC8983440.

Tsai WK, Zettlitz KA, Dahlbom M, Reiter RE, Wu AM. Evaluation of [(131)I]I- and [(177)Lu]Lu-DTPA-A11 Minibody for Radioimmunotherapy in a Preclinical Model of PSCA-Expressing Prostate Cancer. Mol Imaging Biol. 2020 Oct;22(5):1380-1391. doi: 10.1007/s11307-020-01518-4. PubMed PMID: 32661830; PubMed Central PMCID: PMC7688013.

Zettlitz KA, Tsai WK, Knowles SM, Salazar FB, Kobayashi N, Reiter RE, Wu AM. [(89)Zr]A2cDb Immuno-PET of Prostate Cancer in a Human Prostate Stem Cell Antigen Knock-in (hPSCA KI) Syngeneic Model. Mol Imaging Biol. 2020 Apr;22(2):367-376. doi: 10.1007/s11307-019-01386-7. PubMed PMID: 31209779; PubMed Central PMCID: PMC6920577.

Zettlitz KA, Waldmann CM, Tsai WK, Tavaré R, Collins J, Murphy JM, Wu AM. A Dual-Modality Linker Enables Site-Specific Conjugation of Antibody Fragments for (18)F-Immuno-PET and Fluorescence Imaging. J Nucl Med. 2019 Oct;60(10):1467-1473. doi: 10.2967/jnumed.118.223560. Epub 2019 Mar 15. PubMed PMID: 30877181; PubMed Central PMCID: PMC6785789.

Zettlitz KA, Tavaré R, Tsai WK, Yamada RE, Ha NS, Collins J, van Dam RM, Timmerman JM, Wu AM. (18)F-labeled anti-human CD20 cys-diabody for same-day immunoPET in a model of aggressive B cell lymphoma in human CD20 transgenic mice. Eur J Nucl Med Mol Imaging. 2019 Feb;46(2):489-500. doi: 10.1007/s00259-018-4214-x. Epub 2018 Nov 19. PubMed PMID: 30456475; PubMed Central PMCID: PMC6580847.

Richter F, Zettlitz KA, Seifert O, Herrmann A, Scheurich P, Pfizenmaier K, Kontermann RE. Monovalent TNF receptor 1-selective antibody with improved affinity and neutralizing activity. MAbs. 2019 Jan;11(1):166-177. doi: 10.1080/19420862.2018.1524664. Epub 2018 Oct 2. PubMed PMID: 30252601; PubMed Central PMCID: PMC6343807.

Tsai WK, Zettlitz KA, Tavaré R, Kobayashi N, Reiter RE, Wu AM. Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody. Theranostics. 2018;8(21):5903-5914. doi: 10.7150/thno.27679. eCollection 2018. PubMed PMID: 30613270; PubMed Central PMCID: PMC6299441.

Zettlitz KA, Tsai WK, Knowles SM, Kobayashi N, Donahue TR, Reiter RE, Wu AM. Dual-Modality Immuno-PET and Near-Infrared Fluorescence Imaging of Pancreatic Cancer Using an Anti-Prostate Stem Cell Antigen Cys-Diabody. J Nucl Med. 2018 Sep;59(9):1398-1405. doi: 10.2967/jnumed.117.207332. Epub 2018 Mar 30. PubMed PMID: 29602820; PubMed Central PMCID: PMC6126441.

Zettlitz KA, Tavaré R, Knowles SM, Steward KK, Timmerman JM, Wu AM. ImmunoPET of Malignant and Normal B Cells with (89)Zr- and (124)I-Labeled Obinutuzumab Antibody Fragments Reveals Differential CD20 Internalization In Vivo. Clin Cancer Res. 2017 Dec 1;23(23):7242-7252. doi: 10.1158/1078-0432.CCR-17-0855. Epub 2017 Sep 19. PubMed PMID: 28928164; PubMed Central PMCID: PMC5880625.

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