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Bispecific antibodies (BsAbs) are a new group of targeted therapies that are revolutionizing the treatment landscape of B-cell non-Hodgkin's lymphoma (B-NHL). In the relapsed/refractory setting, salvage chemotherapy and autologous stem cell transplantation are capable of curing 50% of patients, whereas the other half will have a dismal outcome with a median overall survival of less than 12 months. This unmet need reinforced the importance of innovative therapies like the BsAbs and CAR-T cell therapies. In this review, we delve into BsAbs in B-NHL from the preclinical development to clinical data in both refractory and frontline settings, and then discuss future perspectives.
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http://dx.doi.org/10.1038/s41408-024-00989-w | DOI Listing |
Genes Dis
November 2025
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
Oncolytic viruses (OVs), a kind of emerging therapeutics for treating tumors, are characterized by high replication efficiency, superior killing effects, and few adverse reactions, which have shown great application prospects in preclinical tumor treatment trials. To overcome the limitations of OV monotherapy, recent studies have found that combination therapy with other anti-tumor therapeutics, especially with immunotherapy, yields promising outcomes in tumor eradication. Due to the advancements in genetic engineering, the combination of OVs with novel immunotherapy, including cellular immunotherapy, adoptive cellular immunotherapy, immune checkpoint inhibitors, cancer vaccines, cytokines, and bi- or tri-specific T cell engagers, has greatly improved clinical outcomes and quality of life of tumor patients.
View Article and Find Full Text PDFAdv Immunol
July 2025
Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab, India. Electronic address:
Lately, the urgency of precision medicine in cancer care through immunotherapy has reformed the arena of oncology. Although immunomodulatory therapeutics in cancer have been preliminarily concentrated on T-cells, emerging evidences have suggested that intra-tumoral B-cells and plasma cells have significant contributions in cancer prognosis primarily through the production of antibodies. B-cell oriented cancer vaccines have been used in early clinical trials of breast and other cancers after multiple preclinical studies.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
June 2025
Paediatric Bone Marrow Transplantation and Cell Therapy Centre, Children's Blood and Cancer Centre, KK Women's and Children's Hospital, SingHealth, Singapore, Singapore.
Despite promising results with chimeric antigen receptor modified T(CAR-T) cells and virus-specific T(VST) cells, both forms of therapy are limited by timely availability, affordability, persistency, and antigen escape. To overcome these barriers, we developed multitargeting hypo-alloimmunogenic CAR-T and VST for off-the-shelf administration. We generated bi-specific CAR-T against CD19 and CD22 and tri-specific VST against S, M, and N proteins of SARS-CoV-2 for real patient use.
View Article and Find Full Text PDFAdv Mater
July 2025
School of Medicine, Nankai University, Tianjin, 300071, China.
T cell engagers, which bind tumor-associated antigens and T cell specific molecules, represent a promising class of immunotherapies for enhancing targeted immune responses. Here, a "plug-and-display" platform is introduced for engineering T cell nanoengagers by anchoring antibody fragments into lipid-based nanoparticles. This approach utilizes a genetically engineered lipoprotein fused with single-chain variable fragments (scFv) and nanobodies, which spontaneously integrate into lipid bilayer of the nanoparticles, achieving a high surface density of at least 0.
View Article and Find Full Text PDFCell Death Discov
February 2025
Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Naples, Italy.
One of the most promising cancer immunotherapies is based on bi-specific T-cell engagers (BiTEs) that simultaneously bind with one arm to a tumor-associated antigen on tumor cells and with the other one to CD3 complex on T cells to form a TCR-MHC independent immune synapse. We previously generated four novel tri-specific tribodies made up of a Fab targeting 5T4, an oncofetal tumor antigen expressed on several types of tumors, a scFv targeting CD3 on T cells, and an additional scFv specific for an immune checkpoint (IC), such as PD-1, PD-L1 or LAG-3. To verify their advantages over the combinations of BiTEs (CD3/TAA) with IC inhibitors, recently used to overcome tumor immunosuppressive environment, here we tested their functional properties in comparison with clinically validated mAbs targeting the same ICs, used alone or in combination with a control bi-specific devoid of immunomodulatory scFvs, called 53 P.
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