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2. Bispecific antibodies for the treatment of breast cancer.

Author

Dillon, Patrick, Lum, Lawrence, and Tushir-Singh, Jogender

Subjects
Bispecific antibody, breast cancer, cellular therapy, clinical trials, immunotherapy, Antibodies, Bispecific, Breast Neoplasms, Female, Humans, Immunotherapy, T-Lymphocytes, Tumor Microenvironment
Abstract

INTRODUCTION: There are more than two dozen bispecific antibodies (BsAbs) in development with a variety of designs which are relevant to breast cancer. The field of BsAbs for breast cancer includes agents that co-direct immune recognition of the cancer cell, target unique cancer antigens, and target the microenvironment. BsAbs are being developed for use as antibody-drug conjugates and as homing signals for engineered T-cells. AREAS COVERED: This review covers potential targets for bispecific antibodies, agents in pre-clinical development, agents in clinical trials, combinatorial therapies, and future directions. EXPERT OPINION: There is no BsAb approval expected for breast cancer in the near term, but late-stage trials are underway. Future BsAb roles in breast cancer are possible given unmet needs in estrogen receptor+ disease, residual disease, and de-escalating chemotherapy use. The HER2+ space shows hints of success for BsAbs, but is already crowded. Areas of unmet need still exist.

Published
2022

3. LIGHT enhanced bispecific antibody armed T-cells to treat immunotherapy resistant colon cancer

Author

Qiao, Guilin, Kone, Lyonell B, Phillips, Evan H, Lee, Steve Seung-Young, Brown, Grace E, Khetani, Salman R, Thakur, Archana, Lum, Lawrence G, Prabhakar, Bellur S, and Maker, Ajay V

Subjects
Immunization, Colo-Rectal Cancer, Vaccine Related, Digestive Diseases, Clinical Research, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Antibodies, Bispecific, CD3 Complex, Colonic Neoplasms, Humans, Immunotherapy, T-Lymphocytes, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Increased tumor infiltrating lymphocytes (TIL) are associated with improved patient responses to immunotherapy. As a result, there is interest in enhancing lymphocyte trafficking particularly to colon cancers since the majority are checkpoint blockade-resistant and microsatellite stable. Here, we demonstrate that activated T-cells (ATC) armed with anti-CD3 x anti-EGFR bispecific antibody increases TIL and mediate anti-tumor cytotoxicity while decreasing tumor cell viability. Furthermore, treatment induces endogenous anti-tumor immunity that resisted tumor rechallenge and increased memory T-cell subsets in the tumor. When combined with targeted tumor expression of the tumor necrosis factor superfamily member LIGHT, activated T-cell proliferation and infiltration were further enhanced, and human colorectal tumor regressions were observed. Our data indicate that tumor-targeted armed bispecific antibody increases TIL trafficking and is a potentially potent strategy that can be paired with combination immunotherapy to battle microsatellite stable colon cancer. SIGNIFICANCE: Enhancing trafficking of tumor infiltrating lymphocytes (TILs) to solid tumors has been shown to improve outcomes. Unfortunately, few strategies have been successful in the clinical setting for solid tumors, particularly for "cold" microsatellite stable colon cancers. In order to address this gap in knowledge, this study combined TNFSF14/LIGHT immunomodulation with a bispecific antibody armed with activated T-cells targeted to the tumor. This unique T-cell trafficking strategy successfully generated anti-tumor immunity in a microsatellite stable colon cancer model, stimulated T-cell infiltration, and holds promise as a combination immunotherapy for treating advanced and metastatic colorectal cancer.

Published
2022

4. Race-related Differences in Sipuleucel-T Response Among Men with Metastatic Castrate-Resistant Prostate Cancer

Author

Heath, Elisabeth I., primary, Thakur, Archana, additional, Chen, Wei, additional, Hwang, Clara, additional, Paller, Channing J., additional, Cackowski, Frank C, additional, Boerner, Julie L., additional, Heilbrun, Lance, additional, Smith, Melanie P., additional, Schalk, Dana L., additional, Schienschang, Amy, additional, Whitaker, Sarah A., additional, Polend, Amanda, additional, Smith, Daryn, additional, Vaishampayan, Ulka N., additional, Dickow, Brenda, additional, and Lum, Lawrence G., additional

Published
2024
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6. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Author

Lundqvist, Andreas, van Hoef, Vincent, Zhang, Xiaonan, Wennerberg, Erik, Lorent, Julie, Witt, Kristina, Sanz, Laia Masvidal, Liang, Shuo, Murray, Shannon, Larsson, Ola, Kiessling, Rolf, Mao, Yumeng, Sidhom, John-William, Bessell, Catherine A, Havel, Jonathan, Schneck, Jonathan, Chan, Timothy A, Sachsenmeier, Eliot, Woods, David, Berglund, Anders, Ramakrishnan, Rupal, Sodre, Andressa, Weber, Jeffrey, Zappasodi, Roberta, Li, Yanyun, Qi, Jingjing, Wong, Philip, Sirard, Cynthia, Postow, Michael, Newman, Walter, Koon, Henry, Velcheti, Vamsidhar, Callahan, Margaret K, Wolchok, Jedd D, Merghoub, Taha, Lum, Lawrence G, Choi, Minsig, Thakur, Archana, Deol, Abhinav, Dyson, Gregory, Shields, Anthony, Haymaker, Cara, Uemura, Marc, Murthy, Ravi, James, Marihella, Wang, Daqing, Brevard, Julie, Monaghan, Catherine, Swann, Suzanne, Geib, James, Cornfeld, Mark, Chunduru, Srinivas, Agrawal, Sudhir, Yee, Cassian, Wargo, Jennifer, Patel, Sapna P, Amaria, Rodabe, Tawbi, Hussein, Glitza, Isabella, Woodman, Scott, Hwu, Wen-Jen, Davies, Michael A, Hwu, Patrick, Overwijk, Willem W, Bernatchez, Chantale, Diab, Adi, Massarelli, Erminia, Segal, Neil H, Ribrag, Vincent, Melero, Ignacio, Gangadhar, Tara C, Urba, Walter, Schadendorf, Dirk, Ferris, Robert L, Houot, Roch, Morschhauser, Franck, Logan, Theodore, Luke, Jason J, Sharfman, William, Barlesi, Fabrice, Ott, Patrick A, Mansi, Laura, Kummar, Shivaani, Salles, Gilles, Carpio, Cecilia, Meier, Roland, Krishnan, Suba, McDonald, Dan, Maurer, Matthew, Gu, Xuemin, Neely, Jaclyn, Suryawanshi, Satyendra, Levy, Ronald, Khushalani, Nikhil, Wu, Jennifer, Zhang, Jinyu, Basher, Fahmin, Rubinstein, Mark, Bucsek, Mark, and Qiao, Guanxi

Subjects
Good Health and Well Being
Published
2016

10. Looking ahead to CD3, T-cell engager bispecific antibodies for hematological malignancies

Author

Reed, Daniel R. and Lum, Lawrence G.

Abstract

ABSTRACTIntroductionSince the approval of the bispecific antibody blinatumomab in 2017 for the treatment of acute lymphoblastic leukemia in relapse, the development of numerous bispecific antibody constructs has dramatically expanded in hematologic malignancies. Many have recently received Food Drug Administration and European Medicines Agency approvals in various stages of treatment for lymphomas, leukemias, and multiple myeloma.Areas coveredThe purpose of this review is to provide an overview of bispecific antibody treatment including the mechanisms leading to effector T cells targeting tumor-associated antigens, the treatment indications, efficacies, toxicities, and challenges of the different constructs. A literature search was performed through access to PubMed and clinicaltrials.gov.Expert opinionWhile there has been substantial success in the treatment of NHL, MM, and ALL, there are still hematologic malignancies such as AML where there has been limited progress. It is important to continue to investigate new designs, tumor antigen targets, and further refine where current approved bispecific antibodies fit in terms of sequencing of therapy. Hopefully, with the knowledge gained in recent years and the explosion of these therapies, patients with blood cancers will continue to benefit from these treatments for years to come.

Published
2024
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11. Targeting GD2-positive Refractory/Resistant Neuroblastoma and Osteosarcoma with Anti- CD3 x Anti-GD2 Bispecific Antibody Armed T cells

Author

Yankelevich, Maxim, primary, Thakur, Archana, additional, Modak, Shakeel, additional, Chu, Roland, additional, Taub, Jeffrey, additional, Martin, Alissa, additional, Schalk, Dana L., additional, Schienshang, Amy, additional, Whitaker, Sara, additional, Rea, Katie, additional, Lee, Daniel W., additional, Liu, Qin, additional, Shields, Anthony, additional, Cheung, Nai-Kong, additional, and Lum, Lawrence G., additional

Published
2023
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12. 723 Metabolically reprogrammed autologous Th1/Tc1 cell therapy (RAPA-201) yields promising safety and efficacy in post-PD-(L)1 solid tumor patients without lymphodepleting host conditioning

Author

Gutierrez, Martin, primary, Donato, Michele, additional, Reich-Slotky, Ronit, additional, Patel, Sunil, additional, Finlay, Morgan, additional, Coordinator, Research Nurse, additional, Lum, Lawrence G, additional, Park, Jee Hyun, additional, Felizardo, Tania, additional, and Fowler, Daniel H, additional

Published
2023
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13. 629-E Randomized trial comparing conventional vs novel treatment planning technique to improve the immune system during lung SBRT

Author

Wijesooriya, Krishni, primary, Larner, James M, additional, Read, Paul W, additional, Showalter, Timothy N, additional, Lum, Lawrence G, additional, Conaway, Mark R, additional, Thakur, Archana, additional, Nguyen, Cam, additional, Lain, David W, additional, Romano, Kara, additional, McLaughlin, Christopher M, additional, Luminais, Christopher K, additional, Janowski, Einsley, additional, Muller, Donald, additional, Ward, Kristin, additional, Dutta, Sunil, additional, Sanders, Jason, additional, Cousins, David, additional, Wood, Song, additional, Chen, Joe, additional, Asare, Ebenezer, additional, Nesbit, Emily, additional, Chavis, Yhana C, additional, and Walker, Kristin V, additional

Published
2023
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18. Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities

Author

Yenerall, Paul, primary, Sung, Tae, additional, Palyada, Kiran, additional, Qian, Jessie, additional, Arat, Seda, additional, Kumpf, Steven W, additional, Wang, Shih-Wen, additional, Biddle, Kathleen, additional, Esparza, Carlos, additional, Chang, Stephanie, additional, Scott, Wesley, additional, Collette, Walter, additional, Winrow, Taylor-Symon, additional, Affolter, Tim, additional, Shirai, Norimitsu, additional, Thibault, Stephane, additional, Wang, Julia, additional, Liu, Ling, additional, Bauchmann, Mary, additional, Frey, Jessica, additional, Steyn, Stefanus, additional, Sacaan, Aida, additional, Vitsky, Allison, additional, Ahn, Youngwook, additional, Paul, Tom, additional, Lum, Lawrence, additional, Oyer, Jon, additional, Yang, Amy, additional, and Hu, Wenyue, additional

Published
2023
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24. Supplementary Data from EGF Receptor and mTORC1 Are Novel Therapeutic Targets in Nonseminomatous Germ Cell Tumors

Author

Chen, Kenneth S., primary, Fustino, Nicholas J., primary, Shukla, Abhay A., primary, Stroup, Emily K., primary, Budhipramono, Albert, primary, Ateek, Christina, primary, Stuart, Sarai H., primary, Yamaguchi, Kiyoshi, primary, Kapur, Payal, primary, Frazier, A. Lindsay, primary, Lum, Lawrence, primary, Looijenga, Leendert H.J., primary, Laetsch, Theodore W., primary, Rakheja, Dinesh, primary, and Amatruda, James F., primary

Published
2023
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30. Data from EGF Receptor and mTORC1 Are Novel Therapeutic Targets in Nonseminomatous Germ Cell Tumors

Author

Chen, Kenneth S., primary, Fustino, Nicholas J., primary, Shukla, Abhay A., primary, Stroup, Emily K., primary, Budhipramono, Albert, primary, Ateek, Christina, primary, Stuart, Sarai H., primary, Yamaguchi, Kiyoshi, primary, Kapur, Payal, primary, Frazier, A. Lindsay, primary, Lum, Lawrence, primary, Looijenga, Leendert H.J., primary, Laetsch, Theodore W., primary, Rakheja, Dinesh, primary, and Amatruda, James F., primary

Published
2023
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31. Supplementary Figure S2 from Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer

Author

Vaishampayan, Ulka N., primary, Thakur, Archana, primary, Chen, Wei, primary, Deol, Abhinav, primary, Patel, Meera, primary, Dobson, Kimberlee, primary, Dickow, Brenda, primary, Schalk, Dana, primary, Schienschang, Amy, primary, Whitaker, Sarah, primary, Polend, Amanda, primary, Fontana, Joseph A., primary, Heath, Elisabeth I., primary, and Lum, Lawrence G., primary

Published
2023
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32. Supplementary Table S2 from Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer

Author

Vaishampayan, Ulka N., primary, Thakur, Archana, primary, Chen, Wei, primary, Deol, Abhinav, primary, Patel, Meera, primary, Dobson, Kimberlee, primary, Dickow, Brenda, primary, Schalk, Dana, primary, Schienschang, Amy, primary, Whitaker, Sarah, primary, Polend, Amanda, primary, Fontana, Joseph A., primary, Heath, Elisabeth I., primary, and Lum, Lawrence G., primary

Published
2023
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33. Data from Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer

Author

Vaishampayan, Ulka N., primary, Thakur, Archana, primary, Chen, Wei, primary, Deol, Abhinav, primary, Patel, Meera, primary, Dobson, Kimberlee, primary, Dickow, Brenda, primary, Schalk, Dana, primary, Schienschang, Amy, primary, Whitaker, Sarah, primary, Polend, Amanda, primary, Fontana, Joseph A., primary, Heath, Elisabeth I., primary, and Lum, Lawrence G., primary

Published
2023
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35. Supplementary Methods and Materials, Tables S1-S6 from Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial

Author

Lum, Lawrence G., primary, Thakur, Archana, primary, Al-Kadhimi, Zaid, primary, Colvin, Gerald A., primary, Cummings, Francis J., primary, Legare, Robert D., primary, Dizon, Don S., primary, Kouttab, Nicola, primary, Maizel, Abby, primary, Colaiace, William, primary, Liu, Qin, primary, and Rathore, Ritesh, primary

Published
2023
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