Subcutaneous delivery of theranostic cell-based therapies

Introduction

This PoC project seeks to develop a simple-to-implement self-assembled and injectable hydrogel material for the controlled co-delivery of our simili-CAR NK cells and stimulatory cytokines to improve treatment of both solid and liquid tumors.

Background

Similar to biologics delivery where monoclonal antibodies (mAbs) are commonly administered by IV infusion due to regulatory criteria favoring such route, which had limited confounding factors, the IV administration remains responsible for some over costs and clinical challenges. These challenges include:

1. The need for dedicated infusion facilities.
2. Aseptic preparation of required infusion batches.
3. Extended infusion times.
4. Potential difficulties and risks with IV catheters.

The subcutaneous (SC) administration is deemed to overcome many of these challenges and might appear as an attractive alternative to the IV administration.

Patient Preferences

In addition, the SC route used for mAb administration was received with overwhelming preference according to patients, despite limited and reversible local adverse events induced by the rHuPH20.

Alternative Solutions

Alternative solutions are being evaluated through clinical trials, such as:

1. The direct SC injection of mAbs without recombinant human hyaluronidase.
2. Using novel enzymes.

However, none are currently being clinically developed for cellular therapies. Moreover, those alternative SC methods induced large pharmacokinetic heterogeneity between patients, confirming the need to develop novel alternative approaches to accelerate the development of SC mAbs formulation.

Proposed Approach

Hence, in parallel to the biological approach, chemistry-based approaches, such as hydrogels, have been proposed. However, to date, none of them have successfully managed to be translated to the clinic. This can be explained by:

• The absence of full biodegradability after injection.
• Potential poor biocompatibility inducing inflammatory responses.

Here, we sought to develop a novel formulation of functionalized chitosans for controlled release of modified NK cells.