JOIN USFighting the cancer pandemic
This World Cancer Day’s theme is ‘Close the Care Gap’. Closing the gap focuses on recognising the power of knowledge and challenges assumptions. Globally, Covid-19 has changed our perspective in a revolutionary way. It has pushed companies over the technology tipping point and transformed business across sectors forever. Probably Covid-19 has accelerated the adoption of digital technologies by several years and looks like it is here to stay. To stay competitive in this new business and economic environment requires new strategies and practices. We have changed our lifestyles, but have we solved this mystery virus?
This has been a setback to the pandemic running in parallel, which is the ‘cancer pandemic’. Patients who would travel across half the world for treatment are stuck with a lack of adequate diagnostic and treatment facilities. Resource deplete towns and smaller cities also with travel restrictions have suffered hugely. There have been delays and a localised disease eventually became advanced. Some patients with advanced cancers also due to compromised immunity were more vulnerable to severe Covid and its consequences. Cancer surgeries and systemic therapies were delayed and this again was detrimental to the overall prognosis.
A notable feature of the Covid-19 pandemic has been the dramatic heterogeneity in clinical presentations and outcomes. Initially, an increase in acute phase reactants like CRP, ESR and also cytokine release may be responsible for acute events but at the same time, excessive host immune response may be responsible for mortality due to Covid and also probably the mechanism in patients with cancer, autoimmune diseases and transplant recipients. Recent research has identified immune signatures associated with severe Covid-19 such as activated CD4, CD8 T cells, plasmablasts and antibody responses. A study on blood cancers was probably a step towards trying to understand this enigma. Cancer patients have increased morbidity and mortality from Coronavirus Infection 2019 (Covid-19). Blood cancers had a significantly higher death rate relative to patients with solid cancers. An important study showed that an immune phenotype characterised by CD8 T cell depletion was associated with a high viral load and the highest mortality. Despite impaired B cell responses, patients with blood cancer and preserved CD8 T cells had a lower viral load and mortality. This data highlights the importance of CD8 T cells in acute Covid-19. A higher CD8 T cell count was associated with improved overall survival in patients with hematologic cancers.
So does the future of oncology care lie in modifying host immunity to fight cancer and also infections like Covid-19? Well, the answer is yes! Cancer immunity is a complex process involving tumour recognition and rejection, immune synapse and immune surveillance. All this is an interplay of CD8 & CD4 T-cells, NK cells and Macrophages. Some approaches include cytokines, manipulation of T cells (checkpoint inhibitors), oncolytic viruses, therapies directed at other cell types, and vaccines. Along with this, there is a new class of immunity modifying drugs called ‘immunotherapy’. Immune checkpoint blockade immunotherapy agents have regulatory approval for multiple clinical indications like renal cell carcinoma, melanoma, lung cancer. PD-1 and CTLA-4 blockade are in standard clinical use which modifies the host response to fight against cancer. Certain markers of predicting their response include tumour mutation burden and PD L1 testing.
Another important pathway is Manipulating T cells or Adoptive T cell transfer. This comes by Chimeric Antigen Receptor (CAR) T cells which are genetically modified T cells and currently used in conditions like Non-Hodgkin’s Lymphoma, ALL etc. Tumour Infiltrating Lymphocytes is another one in this category.
Cancer vaccines are a promising technology that all of us are looking forward to. There is a long history of trying to harness this methodology, however, we have small successes at this juncture. A few examples are peptide vaccines and dendritic cell vaccines which can be autologous (from the patient’s tumour tissue) or could be allogenic/pooled tumour tissue. The only approved vaccine-based therapy for advanced cancer (prostate) is sipuleucel-T which is an autologous dendritic cell cancer vaccine.
With the recognition of tumour-specific and patient-specific immune responses, there is intense interest in the development of therapeutic vaccines against cancer that can bolster host immune responses. This same theory can be used when we are discussing viral infections like Covid besides others. Principles of cancer immunity had made a quantum leap in the way we look at cancer which in principle is an accumulation of genetic alterations.
(The author is the director, medical oncology & hemato-oncology of a chain of hospitals in Bengaluru.)