Example of a simple and scalable manufacturing process for immunomodulatory alpha neutrophils, a specifically designed immuno-cell therapy with direct and indirect anti-cancer activity for solid tumour indications.

Abstract

e14512 Background: Recent findings have demonstrated neutrophils play a key role in tumour control and in facilitating successful responses to cancer immunotherapy. At LIfT Biosciences we have developed the first-in-class, allogeneic, off-the-shelf, stem cell-derived immuno-cell therapy with anti-cancer neutrophil properties. Immunomodulatory Alpha Neutrophils (IMANs) exert their anti-cancer activity via multiple direct and indirect mechanisms, ensuring direct antigen-independent tumour cell killing, as well as impacting anti-cancer function of other direct acting cells such as NK and gamma delta T cells, and further immunomodulation of the environment to boost adaptive immune responses ensuring maximal T cell activity can be achieved. IMANs have the potential to provide major clinical benefits in the treatment of multiple solid tumours. Methods: We present a patent-pending, GMP-compliant manufacturing process starting with CD34+ cells isolated from mobilized peripheral blood of healthy donors. Extensive characterisation of starting material in combination with in-process and raw material controls results in a simple, consistent, scalable manufacturing process using known and established manufacturing platforms. IMANs are granulopoietic myeloid progenitors derived from the expansion of CD34+ cells followed by differentiation in proprietary media compositions, composed of critical priming agents which are known to promote anti-cancer neutrophil phenotype and function. Neutrophil functional heterogeneity is becoming increasingly appreciated and we have designed our manufacturing process to produce activated, committed, persistent IMANs with multimodal mechanisms of action. IMANs are composed of distinct neutrophil progenitor populations. IMANs are cytotoxic towards numerous solid tumour cell lines, expressing tumour-ablating Neutrophil elastase. Furthermore, IMANs exert immunomodulatory properties through cytokine and chemokine secretion, and expression of ligands for T and NK cell co-stimulatory receptors. Results: The manufacturing process has been optimised with vast expansion capacity, showing up to 1000-fold increase from starting cell populations and efficient cryopreservation with exceptional post-thaw recovery. Conclusions: Cryopreserved IMANs offer a cost-effective and globally accessible cell therapy with the potential for long term clinical benefit.