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.

Keywords: antibody combinations; antibody–drug conjugates; bi-specific T cell engager; brentuximab vedotin; cutaneous lymphoma; monoclonal antibodies; nanobioconjugates; photoimmunotherapy; radioimmunotherapy; rituximab.

Figure 1

Drug targets on malignant lymphocytes of T and B cell cutaneous lymphoma and current antibody-directed treatment options. Abbreviations: CCR4 C-C chemokine receptor type 4, CD, cluster of differentiation; CLA, cutaneous lymphocyte antigen; CXCR4/5, C-X-C chemokine receptor type 4/5; LFA-1, lymphocyte function-associated antigen 1 (alphaLbeta2 integrin).