已获批细胞疗法和双特异性抗体在实体瘤中的疗效与安全性：现状

Cancer immunotherapy is a broad term including naked antibodies, bispecific antibodies (BsAbs), immune-checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) therapy, cancer vaccines, activated immune cells, and allogeneic hematopoietic cell transplantation. Recent advances in immune-engaging T-cell therapies have led to significant progress in novel treatments across various cancer types, resulting in prolonged patient survival, mainly in patients with hematologic malignancies. Several CAR T-cell constructs and BsAbs have been approved by regulatory authorities worldwide for relapsed, refractory leukemia, non-Hodgkin lymphoma, and multiple myeloma.

Solid tumors are characterized by an immunosuppressive, fibroinflammatory tumor microenvironment (TME) and immune-suppressive cells, such as regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs).

This, coupled with challenges such as tumor-intrinsic factors (tumor antigen heterogeneity, target antigen loss, hypoxia within the tumor bed, and insufficient preexisting tumor-infiltrating lymphocytes [TILs]) and therapy-related hurdles like on-target off-tumor toxicity, impedes the development of durable immune-engaging T-cell therapies across solid tumor types.

However, a few BsAbs, TILs, and autologous-engineered T-cell receptor (TCR) therapies have recently been approved across indications, paving the way for newer horizons in the solid tumor cellular therapy landscape.

Here, we review the available data on the efficacy and safety of cellular therapies and BsAbs in solid tumors approved thus far by the U. S. Food and Drug Administration. These include BsAbs, TILs, and TCR therapy. Given the lack of homogeneous clinical practice guidelines for TCE therapies in solid tumors, we discuss and compare the efficacy and safety of five therapies.

We further present the therapeutic pipeline across solid tumors and discuss strategies currently under investigation to optimize T-cell subsets to enhance antitumor efficacy while improving the safety profile.