Recent Advancements in Cell-Based Therapies in Melanoma.

Malignant melanoma outcomes have drastically changed in recent years due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients still experience intolerable side effects, therapy resistance, and disease progression on ICI therapy. Therefore, there remains a need for novel therapeutics that address this gap in treatment options. Cell-based therapies have gained wide attention as a therapeutic option that could address this gap in treatment options for advanced melanoma. These therapies work by extracting certain cell types produced in the human body such as T-cells, modifying them based on a specific target, and transfusing them back into the patient. In the realm of cancer therapy, cell-based therapies utilize immune cells to target tumor cells while sparing healthy cells. Recently, the Food and Drug Administration (FDA) has approved the usage of lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, in advanced melanoma. This came following recent results from the C-144-01 study (NCT02360579), which demonstrated the efficacy and safety of TILs in metastatic melanoma patients who otherwise failed on standard ICI/targeted therapy. Thus, the results of this trial as well as the recent FDA approval have proven the viability of utilizing cell-based therapies to fill the gap in treatment options for patients with advanced melanoma. This review aims to provide a comprehensive overview of major cell-based therapies that have been utilized in melanoma by delineating results of the most recent multi-center phase II/ III clinical trials that evaluate the efficacy and safety of major cell-based therapies in melanoma. Additionally, we provide a summary of current limitations in each cell-based therapeutic option as well as a future direction of how to further extrapolate these cell-based therapies in advanced melanoma.

Where Are We Now with Oncolytic Viruses in Melanoma and Nonmelanoma Skin Malignancies?

Skin cancer prognosis has greatly improved recently due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients with advanced skin cancer still experience immunotherapy resistance and disease progression during ICI treatment, thus calling for novel therapeutics which address this treatment gap. Talimogene laherparepvec (T-VEC) has gained popularity in recent years as a viable treatment option for patients with skin cancer. In preclinical studies, T-VEC demonstrated both a direct anti-tumor effect in injected lesions as well as a systemic immune-mediated effect in non-injected lesions, which could pose additional benefits when combined with ICI therapy. Following promising results from the OPTiM trial, the Food and Drug Administration (FDA) approved the usage of T-VEC as a single agent in advanced melanoma. However, the MASTERKEY-265 trial demonstrated that adding T-VEC to pembrolizumab did not offer additional clinical benefit in patients with melanoma. Nevertheless, the promising efficacy of T-VEC and its approval by the FDA helped oncolytic viruses (OVs) gain wide attention in cancer therapy, and extensive research has been undertaken to evaluate the usage of OVs in other tumors such as sarcomas and breast cancers. Here, we provide a review of clinical results from 2022 to 2024 that investigate the efficacy and safety of OVs as a monotherapy or in combination with other therapies in skin malignancies. Furthermore, we delineate the current limitations in OV utilization and outline future directions to enhance clinical outcomes for patients with skin malignancies receiving OV-based therapies.

Clinical efficacy of human split-thickness skin allograft in patients with pyoderma gangrenosum: a case series.

INTRODUCTION: Pyoderma gangrenosum (PG) is an uncommon inflammatory skin disease that is characterized clinically by the development of painful pustules that subsequently progress to large cutaneous ulcers. There is no universally effective treatment for PG, and a combination of local and systemic therapies is often used to manage it. Biologically active, cryopreserved human skin allograft (BSA) has become a standard part of the treatment algorithm for complex nonhealing wounds. These allografts facilitate the wound healing cascade by delivering the essential biologically active compounds of fresh skin to the wound bed and promoting wound bed revascularization. OBJECTIVE: The purpose of this case series was to illustrate how the use of human split-thickness allografts positively contributes to wound healing in patients with PG. CASE PRESENTATIONS: Five cases highlighting the efficacy of a BSA in achieving clinical wound healing in patients with complex PG ulcerations are presented. Clinical findings appear to indicate that the positive effect of BSA in combination with systemic therapies on wound beds in patients with PG is because of a combination of both the unique alterations in the patient's immune system in addition to the possible delays in clearance of cellular components of the allograft, which promote the strong inosculation and revascularization necessary for wound healing. CONCLUSIONS: The BSA studied herein appears to aid in wound healing because it has natural components found in human skin that facilitate wound healing, and it eliminates the potential for pathergy because no graft harvesting from the host is performed. These allografts can be applied numerous times, and each has the major essential components of human skin wound healing for a more rapid and complete epithelialization.