Article
Oncology
Natalya D. Bodyak, Rebecca Mosher, Aleksandr Yurkovetskiy, Mao Yin, Charlie Bu, Patrick R. Conlon, Damon R. Demady, Michael J. DeVit, Dmitry R. Gumerov, Venu R. Gurijala, Winnie Lee, Dennis McGillicuddy, Peter U. Park, Laura L. Poling, Marina Protopova, LiuLiang Qin, Cheri A. Stevenson, Elena Ter-Ovanesyan, Alex Uttard, Dongmei Xiao, Jian Xu, Ling Xu, Donald A. Bergstrom, Timothy B. Lowinger
Summary: Choosing the right target for ADCs is crucial to reduce on-target toxicity. NaPi2b shows promising results in various human tumors, as demonstrated by XMT-1536. The development of a new IHC reagent helps to improve treatment efficacy.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Ryan Ashkar, Darren R. Feldman, Nabil Adra, Mohammad Abu Zaid, Samuel A. Funt, Sandra K. Althouse, Susan M. Perkins, Christin I. Snow, Kayla M. Lazzara, Lina M. Sego, David I. Quinn, Nasser H. Hanna, Lawrence H. Einhorn, Costantine Albany
Summary: Brentuximab vedotin does not exhibit clinically significant single-agent activity in patients with chemo-refractory GCT. Some patients had radiographic stable disease, but no partial or complete responses were observed.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Biochemistry & Molecular Biology
Mateusz A. Krzyscik, Malgorzata Zakrzewska, Vigdis Sorensen, Geir Frode Oy, Skjalg Brunheim, Ellen M. Haugsten, Gunhild M. Maelandsmo, Antoni Wiedlocha, Jacek Otlewski
Summary: Despite being the second leading cause of death worldwide, cancer still lacks a fully effective therapy, highlighting the urgent need for new targeted anticancer drugs. Researchers have developed novel protein-drug conjugates that successfully inhibit tumor growth in a mouse model of human breast cancer.
Review
Oncology
Jesus Fuentes-Antras, Sofia Genta, Abi Vijenthira, Lillian L. Siu
Summary: Antibody-drug conjugates (ADCs) have been approved as anticancer drugs for both solid and hematological malignancies, but only a few have shown survival improvements over standard treatment. The most promising partners for ADCs are those that have additive or synergistic effects on tumor cells without overlapping toxicities. Co-administration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents, and immune checkpoint inhibitors (ICIs) are active candidates. The next generation of ADCs, with tumor-specific targets, improved conjugation technologies, and novel linkers and payloads, brings hope for combinatorial approaches.
Article
Oncology
George D. Demetri, Jason J. Luke, Antoine Hollebecque, John D. Powderly, Alexander Spira, Vivek Subbiah, Louie Naumovski, Chris Chen, Hua Fang, Dominic W. Lai, Huibin Yue, Akshanth R. Polepally, James W. Purcell, Randy Robinson, Padmanee Sharma, James P. Allison, Anthony Tolcher, Victor M. Villalobos
Summary: LRRC15 is a potential therapeutic target expressed in stromal fibroblasts in various solid tumor microenvironments, especially in sarcoma patients. ABBV-085, a LRRC15-targeting antibody-drug conjugate, demonstrated preliminary antitumor activity and safety in sarcoma patients at a dose of 3.6 mg/kg administered every 14 days, with no significant responses observed in other advanced cancer patients at the same dose.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Aureliano Zana, Andrea Galbiati, Ettore Gilardoni, Matilde Bocci, Jacopo Millul, Theo Sturm, Riccardo Stucchi, Abdullah Elsayed, Lisa Nadal, Martina Cirillo, Wolfgang Roll, Lars Stegger, Inga Asmus, Philipp Backhaus, Michael Schaefers, Dario Neri, Samuele Cazzamalli
Summary: This study describes a new drug conjugate that targets tumors and releases effective drugs in the tumor microenvironment, which may be promising for treating human malignancies.
CLINICAL CANCER RESEARCH
(2022)
Review
Biotechnology & Applied Microbiology
Charles Dumontet, Janice M. M. Reichert, Peter D. D. Senter, John M. M. Lambert, Alain Beck
Summary: Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the potency of cytotoxic agents. The technology to develop these agents has improved in past years, but toxicity remains a key issue. This Review provides a broad overview of the recent advances and challenges in ADC development for cancer treatment.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Review
Oncology
Paolo Tarantino, Biagio Ricciuti, Shan M. Pradhan, Sara M. Tolaney
Summary: Improvements in the design of antibody-drug conjugates (ADCs) have reshaped the treatment of advanced-stage solid tumours, but toxicities of ADCs are still a concern. Ongoing efforts are being made to enhance the safety of ADCs, including optimizing dose and treatment schedule, modifying ADC components, identifying predictive biomarkers for toxicities, and developing innovative diagnostic tools.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Immunology
Alice Mac Donald, Delphine Guipouy, William Lemieux, Mario Harvey, Louis-Jean Bordeleau, David Guay, Hugo Romero, Yuanyi Li, Renaud Dion, Kathie Beland, Elie Haddad
Summary: NK cell therapy has the potential to be a universal off-the-shelf option for cancer treatment. However, the limited efficacy of NK cell-based immunotherapies against solid tumors is a major challenge. In this study, targeting the NKG2A/HLA-E immune checkpoint by using CRISPR-mediated KLRC1 gene editing significantly improved NK cell cytotoxicity against HLA-E+ tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Paris Kosti, James W. Opzoomer, Karen Larios-Martinez, Rhonda Henley-Smith, Cheryl L. Scudamore, Mary Okesola, Mustafa Y. M. Taher, David M. Davies, Tamara Muliaditan, Daniel Larcombe-Young, Natalie Woodman, Cheryl E. Gillett, Selvam Thavaraj, John Maher, James N. Arnold
Summary: In this study, a new CAR T cell system utilizing hypoxia-sensing technology for selective expression of pan-ErbB targeted CAR within solid tumors was presented. The approach demonstrated anti-tumor efficacy without off-tumor toxicity, showing potential for expansion of CAR T cell target repertoire for treating solid malignancies.
CELL REPORTS MEDICINE
(2021)
Article
Oncology
Hans-Georg Lerchen, Beatrix Stelte-Ludwig, Melanie Heroult, Dmitry Zubov, Kersten Matthias Gericke, Harvey Wong, Melanie M. Frigault, Amy J. Johnson, Raquel Izumi, Ahmed Hamdy
Summary: The goal of this study was to improve the selectivity of chemotherapy for tumors and reduce side effects. A drug called VIP236 was designed to deliver chemotherapy directly to tumors due to its specific homing feature. In animal models, VIP236 accumulated in tumors and resulted in high and long-lasting tumor regression, as well as reduced metastasis formation in the brain and lungs.
Article
Pharmacology & Pharmacy
Chaitali Passey, Jenna Voellinger, Leonid Gibiansky, Rudy Gunawan, Leonardo Nicacio, Ibrahima Soumaoro, William D. Hanley, Helen Winter, Manish Gupta
Summary: The ADC tisotumab vedotin (TV) has been approved by the US FDA for the treatment of recurrent or metastatic cervical cancer (r/mCC) patients with disease progression after chemotherapy. Population pharmacokinetic modeling was used to evaluate exposure-response relationships and showed that ADC exposure was associated with increased efficacy and safety risks.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Deepthi Ramamurthi, Moola J. Nanjan Chandrasekar, Shanthi B. Santhosh, Sunil K. Patnaik
Summary: Polymers are widely used in drug delivery systems, with polymer-drug conjugates being an effective method for anticancer chemotherapy. Stimuli-responsive polymers such as thermosensitive and pH-sensitive polymers have been used to develop effective drug delivery systems. Elastin-like Polypeptides (ELP) as thermoresponsive polymers have shown potential in anticancer therapy, and can be used in combination with hyperthermia to target drugs to solid tumors.
CURRENT PROTEIN & PEPTIDE SCIENCE
(2021)
Article
Oncology
Jianzheng Wang, Baiwen Zhang, Xiaojiao Cheng, Qingli Li, Huifang Lv, Caiyun Nie, Beibei Chen, Weifeng Xu, Jing Zhao, Yunduan He, Shuiping Tu, Xiaobing Chen
Summary: The study retrospectively analyzed the data of patients with HER2-positive non-breast advanced solid tumors who received pyrotinib-based therapy. The results showed that pyrotinib-based treatment had good antitumor activity and acceptable safety in HER2-positive non-breast advanced solid tumors.
JOURNAL OF ONCOLOGY
(2022)
Review
Pharmacology & Pharmacy
Meghana Kesireddy, Srikanth Reddy Kothapalli, Sai Giridhar Gundepalli, Samia Asif
Summary: Despite progress in cancer treatment, it remains a leading cause of death worldwide. Antibody-drug conjugates (ADCs) combine the properties of chemotherapy and targeted therapy, showing promise as an effective systemic therapy. Currently, there are 13 FDA-approved ADCs for treating various cancers, with new ones in development and clinical trials. This review provides an overview of FDA-approved ADCs, landmark clinical trials, common toxicities, challenges, and future directions.
PHARMACEUTICAL MEDICINE
(2023)