Periodic Reporting for period 1 - CANCER (Personalised Postoperative Immunotherapy To Improving Cancer Outcome and improving quality of life)
Reporting period: 2018-03-01 to 2020-02-29
Our overall objective covers the following four points:
a) to understand the concept of combination of immunotherapy and how it impacts upon cancer treatment;
b) to optimise the biomaterial platform to encapsulate a small library of defined immune reagents for more accurate and timely delivery of the combination payload to its intended target;
c) to optimise the cancer management process by improved treatment options for cancer patients and providing evidence of positive socio-economic outcomes leading to wider patient access to immunotherapy and
d) to explore how to extend the survival rate together with QOL after oncology therapy with respect to healthy eating and adequate exercise in the form of palliative care.
The achievements may be categorised into:
a) research and development of different combination therapies and their impact on cancer immunity,
b) development and testing of different biomaterial plus combination therapy platforms on preclinical models and
c) assessing the socio-economic outcomes leading to wider patient access to immunotherapy and
d) new approaches to palliative care after immunotherapy.
Our CANCER project has developments at the preclinical development phase but already recognition of these clinically approved categories, may well open the door to our own research, where we are already developing and testing photodynamic compounds, novel biomaterials, new vaccine adjuvants, oncolytic viral therapy and fast selection of neo-antigens in different combinations. These also have the breakthrough potential to forge new categories of treatment with respect to cancer immunotherapy based upon our use of new nanomaterials.
There are several important socio-economic impacting factors as a result of our discoveries:
Palliative care after cancer treatment has always followed the model that the patient has had one or a combination of, surgery, radiotherapy, antibody targeted and/or chemotherapy. However, immune checkpoint inhibitors have unique toxicities and response kinetics, which are different to current cytotoxic and gene-targeted anti-cancer agents. The CANCER project’s aim is for cancer immunotherapy to reverse tolerance, rejuvenate the immune system and restore immune homeostasis. The open questions remain as to whether or not we can continually manipulate the immune system. How long do we need to continue immunotherapy for? Are there long-term consequences, e.g. autoimmunity? What about toxicity or resistance to treatment? When do we start thinking about multiple immunotherapies? The success of these agents raises important questions for exactly how and when to integrate palliative care into the care of patients on immunotherapy. In 2010, advanced melanoma had a median overall survival of 6–9 months and less than 20% could expect to be alive at 2 years. Palliative chemotherapy with dacarbazine, the standard of care, did not improve survival. They very much needed palliative care for symptom management, advance care planning and multidisciplinary support to get the best out of their remaining time. However, by 2018, the very same patients, if they receive combination CTLA-4 and PD-1 blocking agents, have a 3-year median survival of 58%. Despite the remarkable success of checkpoint blockers in improving objective response rates in a subset of patients, it has been demonstrated that ≤ 20–30% of tumour patients with non-small cell lung cancer (NSCLC), renal cell carcinoma, and melanoma benefited from CTLA-4 or PD-1 blockade. To further improve on socio-economic impact, we will in the future look into addressing the issue of the non-responders, as they endure high treatment costs and toxicities with little benefit from the treatments. It is currently difficult to identify and distinguish responders / non-responders. To sustain the success that checkpoint blockers have achieved in the treatment of various tumours in clinical settings, specific prognostic indicators would be identified to predict whether a patient would be rescued by immunotherapy.