Regional Injection of CAR-T Cells for the Treatment of Refractory and Recurrent Diffuse Large B Cell Lymphoma: A Case Report

Abstract

Background: Lymphoma is a common hematological malignancy with many subtypes and considerable heterogeneity. Traditional treatments include chemotherapy, radiotherapy, and surgery. Patients with relapsed, refractory or advanced stage lymphoma have a dismal prognosis. In recent years, chimeric antigen receptors (CARs) have been recognized as powerful tools that redirect antigen-specific T cells independent of human lymphocyte antigen (HLA) restriction and specifically kill tumor cells. Satisfactory results with CAR-based treatments have been achieved in relapsed/refractory B cell leukemia/lymphoma. Our center explored the strategy of subcutaneous injections combined with intravenous drip to overcome certain issues.Case Presentation: A patient with stage IV refractory and relapsed diffuse large B cell lymphoma was treated with regional and intravenous CAR-T cells. During the observation period, the temperature of the skin at the abdominal wall mass was slightly elevated, and tolerable pain in the injection area was reported. Imaging showed regional liquefactive necrosis. After the sequential administration of ibrutinib and venetoclax, the abdominal wall mass significantly decreased in size. Conclusion:The regional injection of CAR-T cells might be safe and feasible for the treatment of regional lesions in patients with refractory and relapsed advanced lymphoma.

Effective antitumor activity of 5T4‐specific CAR‐T cells against ovarian cancer cells in vitro and xenotransplanted tumors in vivo

“…(C) Body weight curve of mice avoiding systematic targeting of T cells in normal tissue, further reducing the risk of unnecessary toxicity. 28,29 Moreover, we also found that the systematic delivery of 5T4 CAR-T cells in the subcutaneous injection xenotransplanted model significantly controlled the growth of Skov3 ovarian cancer. Tumor regression quickly appeared 2 weeks after CAR-T cells delivery by tail vein injection.…”

“…delivery shows better curative effect due to it subtly avoids transport restrictions, effectively redistributing 5T4 CAR‐T cells to tumor sites, potentially reducing their systemic distribution, and avoiding systematic targeting of T cells in normal tissue, further reducing the risk of unnecessary toxicity. 28 , 29 …”

Tumor Microenvironment Immunosuppression: A Roadblock to CAR T-Cell Advancement in Solid Tumors

“…One method that has become a common practice in CAR T-cell testing in animal models and clinical trials is injection of CAR T cells into the tumor rather than intravenous delivery. Some improvement of CAR T-cell homing and infiltration in solid tumors has been seen, but it has not shown a complete fix of the problem [ 87 , 88 ].…”

Extending traditional antibody therapies: Novel discoveries in immunotherapy and clinical applications

“…Although the targeted antigen can be expressed in normal tissues, resulting in inadvertent immune-related damage, accumulation of CAR T cells has shown promising tumor eradication in several tissues such as liver, lymph nodes, and bone marrows. [144][145][146] CAR T cell therapy is sometimes combined with chemotherapy or low-dose irradiation regimens that would reduce levels of immuno-suppressive cells (e.g., T regulatory cells, myeloid cells) and increase the likelihood of CAR T cell survival. Brentjens et al 147,148 have experimentally discovered this controversial observation from patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) or relapsed B cell ALL.…”