Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 234-253 http://medscipublisher.com/index.php/cge 239 4.2 Adoptive cell transfer therapies Adoptive cell transfer (ACT) therapies represent a cutting-edge approach in cancer treatment, involving the ex vivo expansion and reinfusion of autologous or allogeneic immune cells with potent anti-tumor activity. This approach aims to overcome the immunosuppressive tumor microenvironment by introducing a large number of activated and tumor-specific immune cells directly into the patient (Galli et al., 2021). 4.2.1 CAR-T cell therapy Chimeric Antigen Receptor T-cell (CAR-T) therapy involves genetically modifying a patient’s T cells to express CARs, which are engineered receptors that combine the antigen-binding domain of a monoclonal antibody with T cell-activating domains. This enables the T cells to specifically recognize and kill cancer cells expressing the target antigen. However, the shortage of TSAs, on-target off-tumour effects, low CAR-T cell infiltration and the immunosuppressive microenvironment are the current research dilemma (Aparicio et al., 2021). In colon cancer, efforts to apply CAR-T therapy have faced challenges due to the immunosuppressive tumor microenvironment and the heterogeneous expression of tumor antigens. However, significant progress is being made in identifying suitable targets such as CEA (carcinoembryonic antigen) and HER2 (human epidermal growth factor receptor 2), which are overexpressed in some colon cancers. Preclinical studies have shown that CAR-T cells targeting these antigens can induce strong anti-tumor responses (Cook et al., 2018). To improve the efficacy and safety of CAR-T therapy in solid tumors, researchers are developing strategies to enhance CAR-T cell persistence, infiltration, and function within the tumor microenvironment (Jin et al., 2021). 4.2.2 TIL therapy Tumor-Infiltrating Lymphocyte (TIL) therapy involves the extraction of TILs from a patient’s tumor, followed by their expansion and activation in vitro before reinfusing them into the patient. TILs are a heterogeneous population of immune cells that have already encountered tumor antigens in vivo, making them highly specific to the patient’s cancer (Zhao et al., 2022). TIL therapy has shown promise in treating metastatic melanoma and is now being explored for other solid tumors, including colon cancer. Clinical trials have demonstrated the potential of TIL therapy in inducing durable responses in patients with refractory solid tumors (Mullard, 2024). For colon cancer, research is focusing on optimizing the protocols for TIL expansion and activation, as well as combining TIL therapy with other treatments such as immune checkpoint inhibitors and targeted therapies to enhance efficacy (Trimaglio et al., 2020). 4.3 Cancer vaccines Cancer vaccines aim to elicit a robust immune response against tumor-specific antigens, leading to the eradication of cancer cells (Saxena et al., 2021; Schiller et al., 2022; Wang et al., 2020a). These vaccines can be categorized into peptide vaccines and dendritic cell (DC) vaccines, among other types. In colon cancer therapy, several promising vaccine strategies have emerged. 4.3.1 Peptide vaccines Peptide vaccines consist of short sequences of amino acids that correspond to tumor-specific antigens. These vaccines are designed to stimulate T cells to recognize and attack cancer cells. One significant advantage of peptide vaccines is their ability to be tailored to individual patients based on their tumor's antigenic profile. Recent advances have focused on identifying and validating novel peptide antigens that can effectively induce an anti-tumor immune response. For instance, studies have identified multiple peptides derived from colon cancer antigens that are capable of activating cytotoxic T lymphocytes (CTLs), leading to targeted killing of cancer cells (Liang et al., 2021; Naciute et al., 2020). 4.3.2 Dendritic cell vaccines Dendritic cell (DC) vaccines leverage the natural ability of DCs to process and present antigens to T cells, thereby initiating a robust immune response. These vaccines involve loading patient-derived DCs with tumor antigens ex vivo and then re-infusing them into the patient. This process enhances the body's immune response to the cancer.
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==