PMPC-PDPA polymersomes for intra-tumoral immunotherapy

Lead Research Organisation: University College London
Department Name: Chemistry

Abstract

We are evaluating the possibility to create new formulations of nanomaterials that target tumour associated immune cells and trigger a immunological response to treat both local and remotely tumour cells. We are thus preparing new formulation of tumour associated antigens with PMPC-PDPA polymersomes and along side developing new phenotypic nanomedicines to target immune-check point process to both instil an antumoral immune response and at the same time stops the tumour ability to inhibit the immune system. The student will be developing new materials; the synthesis and preparation of novel antigen loaded polymersome as well as multivalent and multiplex nanomedicine. This is well within the theme Healthcare technologies and particularly the sub-theme Developing Future Therapies: Supporting the development of novel therapies with technologies to enhance efficacy, minimise costs and reduce risk to patients.
We also will be using concepts from area typical under the EPS areas of Chemical Biology and Biological Chemistry, Polymeric Materials, Soft Matter and Biological Physics as well as Biomateirals and Tissue Engineering

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513143/1 01/10/2018 30/09/2023
2094069 Studentship EP/R513143/1 05/11/2018 04/11/2022 Barbara Ibarzo Yus
 
Description During the period of my PhD I have managed to generate nanoparticle based formulations (a.k.a. polymersomes) made out of a synthetic polymers (namely PMPC-PDPA) , encapsulating proteins that may have the potential to be used as vaccine vehicles, improving the outcomes of the immunisations.

The formulations effectivity as vaccines has been assessed in the context of a mouse tumour model (melanoma, B16-OVA), and immunisations against it using PMPC-PDPA formulations encapsulating the protein of interest (OVA) have proven to elicit extended survival of the animals, as well as to slow the tumour growth rates. Analyses of the immune response within the tumours and the lymph nodes (which are organelles critical for the elicitation of the immune response) have proven that vaccinated animals with PMPC-PDPA polymersomes encapsulating OVA present higher infiltration of lymphocytes within the tumour mass. Besides, antibody titters in blood have proven to be of a 100-fold higher magnitude when immunising animals using polymersomes as opposed to immunisations performed with free protein.

The mechanisms by which more efficient immunisations are being achieved Is yet to be elucidated and experiments are being performed studying the immune cell subsets populations that the polymersomes target in the lymph nodes. Besides, we would like to translate our findings to a colorrectal tumour model, also in mice, which can be more translatable to the clinic. To this end, the plan for the last stage of my research will be to optimise the encapsulation of neoantigens in PMPC-PDPA Polymersomes and carry on performing in vivo studies in order to understand how the polymersomes can enhance immunisations.
Exploitation Route If this model is optimised the use of PMPC-PDPA POs could be translated of other type of vaccines, ie. pathogens. Besides, also in the tumours immunotherapy field, vaccines with these formulations could be used in combination with other immunotherapies nowadays in the clinic, like checkpoint inhibitors.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology