Chimeric antigen receptor (CAR)-T and T-cell receptor (TCR)-engineered T-cell (TCR-T) therapies have revolutionized the treatment of hematological malignancies; however, their application to solid tumors remains a formidable challenge. The immunosuppressive tumor microenvironment, antigen heterogeneity, and manufacturing complexity limit the clinical efficacy and scalability of these treatment modalities. This review provides a comprehensive analysis of the current clinical development strategies for CAR-T and TCR-T cell therapies for solid tumors. Herein, we discuss recent breakthroughs and highlight the potential of TCR-T cell therapy. Furthermore, innovative approaches for enhancing CAR-T cell function in solid tumors (e.g., in vivo engineering; induced pluripotent stem cell-derived allogeneic CAR-T cells; armored CAR constructs; dual-antigen targeting; and combination regimens with checkpoint inhibitors, chemotherapy, radiotherapy, and oncolytic viruses) are explored. We also present trends in global patent activity, revealing a marked acceleration in CAR-T- and TCR-T-related innovations, with the United States and China leading with respect to application volumes. This field is increasingly characterized by multidisciplinary collaborations between academia and industry, driving the development of next-generation platforms, including messenger RNA-based and off-the-shelf cell therapies. Although no CAR-T product has been approved for solid tumors, these findings underscore the accelerating momentum and translational promise of adoptive cell therapies. Addressing the unique biological and logistical challenges of solid tumors is essential for realizing the full potential of these transformative immunotherapies.

BACKGROUND: To examine the efficacies of S-1 and FOLFOX as third-line treatment for patients with advanced pancreatic cancer. METHODS: We retrospectively analyzed the electronic medical record data of patients who received nanoliposomal-irinotecan+5-fluorouracil/leucovorin (nal-IRI+5FU/LV) as second-line treatment after first-line gemcitabine+nab-paclitaxel (GEM+nab-PTX) at the National Cancer Center Hospital (Tokyo, Japan) between June 2020 and May 2023. RESULTS: In total, 100 patients were included, 41 of whom received S-1 (n=19) or FOLFOX (n=22) as third-line therapy. The median age of patients who received S-1 and FOLFOX was 74 (range: 56–85) and 76 (46–81) years. The number of females, those with performance status (PS) 0, those with PS 1, and those with adenocarcinoma histology who received S-1/FOLFOX were 8/14, 6/11, 13/11, and 18/20. Median progression-free survival (PFS), median overall survival (OS), objective response rate, and disease control rate for S-1/FOLFOX were 2.8/2.2 months, 4.4/5.1 months, 0/0%, and 36.8/27.3%, the most common grade ≥3 adverse events were anemia (4/1) and elevated alanine transaminase levels (1/3). Adverse events were consistent with the known limits, and there were no treatment-related deaths. CONCLUSIONS: In patients with advanced pancreatic cancer treated with GEM+nab-PTX, followed by nal-IRI+5FU/LV, third-line treatment with S-1 or FOLFOX was tolerable. However, further therapeutic development is warranted because these regimens have only modest activities.

Background: Adenoid cystic carcinoma (ACC) is the second most common and treatment‐resistant salivary gland carcinoma (SGC). Although platinum‐based therapies are effective, the efficacy of eribulin, a microtubule inhibitor with an 18% response rate in a Phase II trial involving recurrent/metastatic SGC, in patients with advanced ACC after platinum therapy remains unclear.Methods: We retrospectively analyzed 19 patients with unresectable/metastatic ACC treated with platinum‐based therapy between December 2015 and January 2023 at the National Cancer Center Hospital, Japan. Ten patients received eribulin.Results: The median age was 61 years. 84% achieved disease control with the first‐line or later platinum‐based therapy (median progression‐free survival [mPFS]: 7.6 months). Second‐line or later eribulin monotherapy yielded a 50% disease control rate, with mPFS of 3.7 months and median overall survival of 41.7 months. The adverse events, predominantly neutropenia, were manageable.Conclusion: Eribulin shows promising effects of unresectable/metastatic ACC, offering tolerable adverse events.