Cutaneous Lymphoma and Antibody-Directed Therapies

Abstract

The introduction of monoclonal antibodies such as rituximab to the treatment of cancer has greatly advanced the treatment scenario in onco-hematology. However, the response to these agents may be limited by insufficient efficacy or resistance. Antibody–drug conjugates are an attractive strategy to deliver payloads of toxicity or radiation with high selectivity toward malignant targets and limited unwanted effects. Primary cutaneous lymphomas are a heterogeneous group of disorders and a current area of unmet need in dermato-oncology due to the limited options available for advanced cases. This review briefly summarizes our current understanding of T and B cell lymphomagenesis, with a focus on recognized molecular alterations that may provide investigative therapeutic targets. The authors reviewed antibody-directed therapies investigated in the setting of lymphoma: this term includes a broad spectrum of approaches, from antibody–drug conjugates such as brentuximab vedotin, to bi-specific antibodies, antibody combinations, antibody-conjugated nanotherapeutics, radioimmunotherapy and, finally, photoimmunotherapy with specific antibody–photoadsorber conjugates, as an attractive strategy in development for the future management of cutaneous lymphoma.

Role of IL-4 and IL-13 in Cutaneous T Cell Lymphoma

“…Emerging evidence suggests a role in CTCL for additional players in Th2 responses, such as the OX40-OX40L immune checkpoint [82], and novel agents are in clinical development, such as the anti-OX40L amlitelimab (NCT05769777) (Table 1). According to the authors' perspective, future drug development in CTCL should also consider antibody-drug conjugates, capable of selectively delivering cytotoxic molecules towards surface receptors-such as 13Ralpha2-that are highly expressed by malignant skin-homing lymphocytes [83].…”