Call for collaboration on in vivo NK cell-based immune interventions

N(atural)K(iller) cell-based immune interventions are causing a great deal of excitement and have strengthened the belief that NK cells can effectively contribute to fighting infectious diseases or controlling cancer. Several studies provide compelling evidence of antigen-specific recall responses of memory NK cells but the molecular interactions between NK cell receptors and cognate pathogen-associated motifs, or patterns thereof, remain largely unknown.

Scientists increasingly acknowledge that an improved understanding of the mechanisms that enable prolonged immune recognition of pathogen-associated motifs by a diversified spectrum of memory NK cells may enhance the efficacy of NK cell-based immunotherapies and even pave the way to NK cell vaccines against infectious, immune-mediated or tumor diseases. The notion that NK cells could possess an alternative ligand-sensing system is particularly intriguing and may require the scientific and medical community to re-think approaches to investigating NK cell-based immune responses and triggering NK cells to recognize and target infected or otherwise pathologically altered cells. Hence, the time has come for vaccinologists to learn from immunologists to further explore and exploit immunization strategies that harness NK cells to acquire adaptive immune features and eliminate such infected, transformed or otherwise pathologically altered host target cells.

Over the past decade, my focus has been on exploring how NK cell immunology could be harnessed to address a major medical need and significant gap in current vaccinology: equipping our natural and innate first line of immune defense with adaptive immune features. Based on promising proof-of-concept data, I am confident that simple, safe, and highly cost-effective constructs can be developed to educate NK cells in vivo, enabling them to acquire pathogen-specific cytolytic activity and adaptive memory. Guided by immunological principles, I view this novel approach as a more rational and natural path to immunization, laying the groundwork for the next generation of in vivo prophylactic and therapeutic immune interventions.

I tend to believe that the interaction of this novel type of immunocompetent constructs with host cells generates molecular patterns capable of clustering natural cytotoxicity receptors (NCRs) in ways that trigger NK cells to target a multitude of conserved, pathogen-associated motifs through their epigenetic reprogramming (‘training’). I cautiously believe that this mechanism could even harness the host’s innate immune system to protect against all SARS-CoV-2 variants, regardless of previous vaccination.

I am reaching out to scientists - for logistical reasons, preferably in Europe -  who are interested in collaborating on this groundbreaking concept and help me  determine the immunological potential of these new constructs. Specifically, I am seeking research groups with extensive experience in the functional and phenotypic characterization of NCRs on NK cells, including the versatile expression of NCRs and the impact thereof on NK cell-mediated cytotoxicity and IFN-γ secretion.

The objective of this collaboration is to share critical knowledge, experience and insights on mechanisms enabling in vivo education of NK cell-mediated immune recognition of pathogenic agents. I am currently in the process of applying for philanthropic funding with the goal of providing global access if the results from previous in vitro experiments and in vivo challenge experiments in animals can be corroborated.

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