Chemokines as adjuvants for immunotherapy: implications for immune activation with CCL3

ABSTRACT

Introduction: Immunotherapy embodies any approach that manipulates the immune system for therapeutic benefit. In this regard, various clinical trials have employed direct vaccination with patient-specific dendritic cells or adoptive T cell therapy to target highly aggressive tumors. Both modalities have demonstrated great specificity, an advantage that is unmatched by other treatment strategies. However, their full potential has yet to be realized.

Areas covered: In this review, we provide an overview of chemokines in pathogen and anti-tumor immune responses and discuss further improving immunotherapies by arming particular chemokine axes.

Expert commentary: The chemokine macrophage inflammatory protein-1 alpha (MIP-1α, CCL3) has emerged as a potent activator of both innate and adaptive responses. Specifically, CCL3 plays a critical role in recruiting distinct immune phenotypes to intratumoral sites, is a pivotal player in regulating lymph node homing of dendritic cell subsets, and induces antigen-specific T cell responses. The recent breadth of literature outlines the various interactions of CCL3 with these cellular subsets, which have now served as a basis for immunotherapeutic translation.

KEYWORDS:

• Chemokines
• macrophage inflammatory protein-1 alpha
• MIP-1a
• CCL3
• immunotherapy
• antitumor
• antigen-specific T cell
• dendritic cell

Declaration of interest

KA Batich and JH Sampson are co‐inventors on a patent related to the use of Td pre‐conditioning and CCL3 as a method to improve immunization efficacy. The remaining authors declare no competing financial interests. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by the NIH R01 (R01NS099463-01, J.H. Sampson) and F30 NRSA (F30-CA180411-01, K.A. Batich) funding sources and fellowships from the Boehringer Ingelheim Fonds (T.H. Schaller).