Reformation in chimeric antigen receptor based cancer immunotherapy: Redirecting natural killer cell

Natural killer (NK) cells are an important subset of lymphocytes which play a critical role in host immunity against cancers. With MHC-independent recognition, short lifespan and potent cytotoxicity, NK cells make a promising candidate for chimeric antigen receptor (CAR)-engineered cancer immunotherapy. Due to innate biological properties of NK cells, CAR-NK may outperform CAR-T therapy in terms of less side effects and more universal access, which may become a great reformation in CAR-based cancer immunotherapy. The CARs used in peripheral blood (PB) NK cells as well as NK cell line like NK-92 are the most important outfits defining antigenic specificity. The constructs of CARs used in NK cells from different sources vary, which all undergo generational optimization. The anti-tumor effects of CAR-NK have been validated in numerous preclinical trials for cancers, including hematologic malignancies and many solid tumors, which provide evidence for potential clinical application of CAR-NK. Additionally, this review concludes the challenges faced in the application of CAR-NK. Although CAR-NK is considered as one of the most possible “off-the-shelf” products, the improvement for the efficiency of expansion and transduction as well as the solution for underlying safety issues is still needed. Possible coping strategies for challenges and upgrades in techniques are also highlighted for future development in CAR-NK cancer immunotherapy.     

Proteomic analysis of B-cell malignancies

The identification of proteins aberrantly expressed in malignant B-cells can potentially be used to develop new diagnostic, prognostic or therapeutic targets. Proteomic studies of B-cell malignancies have made significant progress, but further studies are needed to increase our coverage of the B-cell malignant proteome. To achieve this goal we stress the advantages of using sub-cellular fractionation, protein separation, quantitation and affinity purification techniques to identify hitherto unidentified signalling and regulatory proteins. For example, proteomic analysis of B-cell plasma membranes isolated from patients with mantle cell lymphoma (MCL) identified the voltage-gated proton channel (HVCN1,[1]). This protein has now been characterised as a key modulator of B-cell receptor (BCR) signalling and abrogation of HVCN1 function could have a role in the treatment of B-cell malignancies dependent on maintained BCR signalling [2]. Similarly, proteomic studies on cell lysates from prognostic subtypes of CLL, distinguished by the absence (UM-CLL) or presence (M-CLL) of somatic hypermutation of the immunoglobulin heavy chain locus identified nucleophosmin 1 (NMP1) as a potential prognostic marker [3,4]. Thus, targeted proteomic analysis on selected organelles or sub-cellular compartments can identify novel proteins with unexpected localisation or function in malignant B-cells that could be developed for clinical purposes.