Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to treat patients. Its diverse TCR clonality, superior tumor-homing ability, and low off-target toxicity endow TIL therapy unique advantages in treating solid tumors compared with other adoptive cellular therapies. Nevertheless, the successful application of TIL therapy currently is still limited to several types of tumors. Herein in this review, we summarize the fundamental work in the field of TIL therapy and the current landscape and advances of TIL clinical trials worldwide. Moreover, the limitations of the current TIL regimen have been discussed and the opportunities and challenges in the development of next-generation TIL are highlighted. Finally, the future directions of TIL therapy towards a broader clinical application have been proposed.

Anticancer-targeted therapies inhibit various kinases implicated in cancer and have been used in clinical settings for decades. However, many cancer-related targets are proteins without catalytic activity and are difficult to target using traditional occupancy-driven inhibitors. Targeted protein degradation (TPD) is an emerging therapeutic modality that has expanded the druggable proteome for cancer treatment. With the entry of new-generation immunomodulatory drugs (IMiDs), selective estrogen receptor degraders (SERDs), and proteolysis-targeting chimera (PROTAC) drugs into clinical trials, the field of TPD has seen explosive growth in the past 10 years. Several challenges remain that need to be tackled to increase successful clinical translation of TPD drugs. We present an overview of the global landscape of clinical trials of TPD drugs over the past decade and summarize the clinical profiles of new-generation TPD drugs. In addition, we highlight the challenges and opportunities for the development of effective TPD drugs for future successful clinical translation.

Drug conjugates are conjugates comprising a tumor-homing carrier tethered to a cytotoxic agent via a linker that are designed to deliver an ultra-toxic payload directly to the target cancer cells. This strategy has been successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce their toxic side effects. Drug conjugates are being developed worldwide, with the potential to revolutionize current cancer treatment strategies. Antibody-drug conjugates (ADCs) have developed rapidly, and 14 of them have received market approval since the first approval event by the Food and Drug Administration in 2000. However, there are some limitations in the use of antibodies as carriers. Other classes of drug conjugates are emerging, such as targeted drugs conjugated with peptides (peptide-drug conjugates, PDCs) and polymers (polymer-drug conjugates, PolyDCs) with the remaining constructs similar to those of ADCs. These novel drug conjugates are gaining attention because they overcome the limitations of ADCs. This review summarizes the current state and advancements in knowledge regarding the design, constructs, and clinical efficacy of different drug conjugates.

Bispecific antibodies (bsAb) that target two independent epitopes or antigens have been extensively explored in translational and clinical studies since they were first developed in the 1960s. Many bsAbs are being tested in clinical trials for treating a variety of diseases, mostly cancer. Here, we provide an overview of various types of bsAbs in clinical studies and discuss their targets, safety profiles, and efficacy. We also highlight the current challenges, potential solutions, and future directions of bsAb development for cancer treatment.