Article
Biochemistry & Molecular Biology
Marit J. van Elsas, Johan M. S. van der Schoot, Alexander Bartels, Kas Steuten, Duco van Dalen, Zacharias Wijfjes, Carl G. Figdor, Thorbald van Hall, Sjoerd H. van der Burg, Martijn Verdoes, Ferenc A. Scheeren
Summary: Regulatory T cells play a crucial role in immune suppression and pose challenges in cancer therapy. By optimizing the Fc domain of an antibody, efficient depletion of tumor-resident regulatory T cells can be achieved. Using a genome engineering strategy, a stable cell line producing optimized antibodies was generated, leading to effective depletion of tumor-resident regulatory T cells and enhanced tumor eradication when combined with other antibodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
David S. Hong, Olivier Rixe, Vi K. Chiu, Patrick M. Forde, Tomislav Dragovich, Yanyan Lou, Asha Nayak-Kapoor, Rom Leidner, James N. Atkins, Agron Collaku, Floyd E. Fox, Margaret A. Marshall, Anthony J. Olszanski
Summary: This study evaluated the safety and efficacy of the combination of mogamulizumab and nivolumab in patients with locally advanced or metastatic solid tumors. The results showed that the combination therapy was well tolerated but did not improve efficacy.
CLINICAL CANCER RESEARCH
(2022)
Article
Engineering, Biomedical
Julian F. Ashby, Julien Schmidt, K. C. Neelima, Armand Kurum, Caroline Koch, Alexandre Harari, Li Tang, Sam H. Au
Summary: This study presents a novel microfluidic approach based on fluid shear stress to identify and recover highly potent T cell clones through probing cellular avidity. The method demonstrates efficient and rapid recovery of high-purity T cells from mixed populations, and markers of cytotoxicity, activation, and avidity persist upon exposure to fresh tumor cells.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Immunology
Mariela A. Moreno Ayala, Timothy F. Campbell, Chenyu Zhang, Noa Dahan, Alissa Bockman, Varsha Prakash, Lawrence Feng, Theo Sher, Michel DuPage
Summary: Infiltration of regulatory T cells into solid cancers via CXCR3 chemokine receptor disrupts dendritic cell-Treg cell interactions and enhances anti-tumor immune response, particularly when combined with anti-PD-1 checkpoint blockade immunotherapy.
Article
Multidisciplinary Sciences
Yuka Maeda, Hisashi Wada, Daisuke Sugiyama, Takuro Saito, Takuma Irie, Kota Itahashi, Kodai Minoura, Susumu Suzuki, Takashi Kojima, Kazuhiro Kakimi, Jun Nakajima, Takeru Funakoshi, Shinsuke Iida, Mikio Oka, Teppei Shimamura, Toshihiko Doi, Yuichiro Doki, Eiichi Nakayama, Ryuzo Ueda, Hiroyoshi Nishikawa
Summary: Despite successful elimination of regulatory T cells with the anti-CCR4 monoclonal antibody, mogamulizumab, clinical improvement remains minimal in patients with solid tumors due to unintended depletion of central memory CD8(+) T cells. These central memory CD8(+) T cells play important roles in the antitumor immune response, and dosage refinement of mogamulizumab may be necessary to avoid depletion of effector components during immune therapy.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Alice Mariottini, Paolo A. Muraro, Jan D. Luenemann
Summary: Development of disease-modifying therapies for multiple sclerosis, such as monoclonal antibody-based cell depletion therapies, has been successful in eliminating pathological immune cell components and promoting the reconstitution of a healthy immune system.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Brianna M. Lax, Joseph R. Palmeri, Emi A. Lutz, Allison Sheen, Jordan A. Stinson, Lauren Duhamel, Luciano Santollani, Alan Kennedy, Adrienne M. Rothschilds, Stefani Spranger, David M. Sansom, K. Dane Wittrup
Summary: Anti-CTLA-4 antibodies have limited long-term benefit in tumor regression. We engineered a nonantagonistic CTLA-4 binding domain and found that both CTLA-4 antagonism and intratumoral Treg depletion are needed for maximum efficacy in anti-CTLA-4 therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Yuma Sakamoto, Takashi Ishida, Ayako Masaki, Takayuki Murase, Eiichi Ohtsuka, Morishige Takeshita, Reiji Muto, Hiromi Iwasaki, Asahi Ito, Shigeru Kusumoto, Nobuaki Nakano, Masahito Tokunaga, Kentaro Yonekura, Yukie Tashiro, Shinsuke Iida, Atae Utsunomiya, Ryuzo Ueda, Hiroshi Inagaki
Summary: This study found that CCR7 gene alterations are significantly associated with survival rates in adult T-cell leukemia/lymphoma (ATL) patients receiving mogamulizumab treatment. However, CCR7 alterations have no significant impact on overall survival in the entire cohort or on patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, patients with CCR4 alterations but lacking CCR7 alterations have significantly better survival rates after receiving mogamulizumab-containing treatments.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Cell Biology
Mariana O. Diniz, Anna Schurich, Senthil K. Chinnakannan, Marion Duriez, Kerstin A. Stegmann, Jessica Davies, Stephanie Kucykowicz, Kornelija Suveizdyte, Oliver E. Amin, Frances Alcock, Tamsin Cargill, Eleanor Barnes, Mala K. Maini
Summary: This study demonstrates that NK cell depletion enhances the immune response to vaccines in a mouse model of chronic HBV infection. It was found that the up-regulation of PD-L1 on liver-resident NK cells and PD-1 on intrahepatic T cells plays a negative regulatory role in the response to therapeutic vaccination. Combining cytokine activation with PD-L1 blockade can convert NK cells into efficient helpers, boosting the CD8(+) T cell response to therapeutic vaccination.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Nicky A. Beelen, Merel R. Aberle, Virginia Bruno, Steven W. M. Olde Damink, Gerard M. J. Bos, Sander S. Rensen, Lotte Wieten
Summary: This study evaluated the cytotoxic potential of adoptive NK cells against pancreatic cancer organoids and found that ADCC-inducing antibodies can enhance NK cell anti-tumor responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Rim Trad, Walid Warda, Vincent Alcazer, Mathieu Neto da Rocha, Ana Berceanu, Clementine Nicod, Rafik Haderbache, Xavier Roussel, Yohan Desbrosses, Etienne Daguindau, Florain Renosi, Christophe Roumier, Lucie Bouquet, Sabeha Biichle, Melanie Guiot, Evan Seffar, Denis Caillot, Stephane Depil, Eric Robinet, Yahya Salma, Eric Deconinck, Marina Deschamps, Christophe Ferrand
Summary: This study identified IL-1RAP as a potential target for AML treatment, as it is overexpressed on the surface of leukemic stem cells (LSCs). The researchers demonstrated the effectiveness of IL-1RAP CAR T-cell therapy against AML cell lines and primary cells from patients, suggesting it as a promising strategy for AML treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Research & Experimental
Liyan Li, Qianwei Miao, Fanqiang Meng, Baoqi Li, Tianyuan Xue, Tianliang Fang, Zhirang Zhang, Jinxie Zhang, Xinyu Ye, Yang Kang, Xingding Zhang, Qian Chen, Xin Liang, Hongbo Chen, Xudong Zhang
Summary: By overexpressing CD64 on cell membrane nanovesicles and encapsulating PD-L1 antibody and chemotherapeutic agent CP, the CD64-NVs-aPD-L1-CP can simultaneously disrupt the immunosuppressive effect of PD-L1, decrease the inhibition of Tregs, enhance the tumor elimination by T cells, suppress tumor growth, and extend survival time, making them charismatic carriers for combined cancer immunotherapy.
Article
Biochemistry & Molecular Biology
Patricia Himmels, Thi Thu Thao Nguyen, Maresa Caunt Mitzner, Alfonso Arrazate, Stacey Yeung, Jeremy Burton, Robyn Clark, Klara Totpal, Raj Jesudason, Angela Yang, Margaret Solon, Jeffrey Eastham, Zora Modrusan, Joshua D. Webster, Amy A. Lo, Robert Piskol, Weilan Ye
Summary: Preclinical and clinical studies show that T cell-dependent bispecific antibodies (TDBs) not only kill tumors but also cause systemic changes, leading to adverse events. In this study, the acute responses to TDBs in tumor-bearing mice were characterized in detail. The results reveal rapid and significant accumulation of lymphocytes and activation of endothelial cells (ECs) around large blood vessels in normal organs, particularly the liver. It is suggested that differential responses in normal tissues and tumors may be attributed to organ-specific ECs, and a list of genes selectively upregulated in large liver vessels by TDBs is identified. Furthermore, the study demonstrates that CD9 facilitates the interaction between T cells and ECs through the support of ICAM-1 in response to soluble factors released from TDB-mediated cytotoxic reactions. These findings provide insights into the response of different vascular beds to cancer immunotherapy and may contribute to improving their safety and efficacy.
Article
Oncology
Khalid W. Kalim, Jun-Qi Yang, Mark Wunderlich, Vishnu Modur, Phuong Nguyen, Yuan Li, Ting Wen, Ashley Kuenzi Davis, Ravinder Verma, Qing Richard Lu, Anil G. Jegga, Yi Zheng, Fukun Guo
Summary: Targeting Cdc42 in Treg cells has shown promising therapeutic potential in cancer immunotherapy, by enhancing antitumor T-cell immunity without triggering autoimmune reactions. This approach involves inducing Treg cell instability through Cdc42 targeting, leading to improved immune responses against tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Rui Zhang, Jinlin Miao, Ping Zhu
Summary: Regulatory T (Treg) cells are crucial in maintaining immune homeostasis and are involved in various diseases, particularly autoimmune diseases. Understanding the heterogeneity of Treg cells can provide new insights for selective therapeutic manipulation and treatment of these diseases.
AUTOIMMUNITY REVIEWS
(2021)
