Manipulating NK cellular therapy from cancer to invasive fungal infection: promises and challenges

Front Immunol. 2023 Jan 11:13:1044946. doi: 10.3389/fimmu.2022.1044946. eCollection 2022.

Abstract

The ideal strategy to fight an infection involves both (i) weakening the invading pathogen through conventional antimicrobial therapy, and (ii) strengthening defense through the augmentation of host immunity. This is even more pertinent in the context of invasive fungal infections whereby the majority of patients have altered immunity and are unable to mount an appropriate host response against the pathogen. Natural killer (NK) cells fit the requirement of an efficient, innate executioner of both tumour cells and pathogens - their unique, targeted cell killing mechanism, combined with other arms of the immune system, make them potent effectors. These characteristics, together with their ready availability (given the various sources of extrinsic NK cells available for harvesting), make NK cells an attractive choice as adoptive cellular therapy against fungi in invasive infections. Improved techniques in ex vivo NK cell activation with expansion, and more importantly, recent advances in genetic engineering including state-of-the-art chimeric antigen receptor platform development, have presented an opportune moment to harness this novel therapeutic as a key component of a multipronged strategy against invasive fungal infections.

Keywords: adoptive cellular therapy; augmentation; chimeric antigen receptor; cytokines; innate immunity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunotherapy, Adoptive / methods
  • Invasive Fungal Infections* / therapy
  • Killer Cells, Natural
  • Neoplasms*
  • Receptors, Chimeric Antigen* / genetics

Substances

  • Receptors, Chimeric Antigen

Grants and funding

BO was supported by the Singapore National Medical Research Council Research Training Fellowship NMRC/RTF/MOH/000616. LYAC was supported by the Clinician Scientist Awards (CSA Senior Investigator and Investigator), Individual Research Grant (IRG), Bedside and Bench (B&B) Grants, Centre Grant, and the Training Fellowship Award from the National Medical Research Council (NMRC), Singapore. LYAC also acknowledges the Aspiration Grant and Summit Research Program, iHealthtech Grant, Bench to Bedside Grant, and Seed Fund from the National University Health System, Infectious Diseases and Synthetic Biology Translational Research Program of the National University of Singapore, as well as the Synthetic Biology Research and Development Program of the National Research Foundation, Singapore.