Chimeric Antigen Receptor T-cell based cellular therapies for cancer: An introduction and Indian perspective.

Using one's own immune system for curing cancer has been an active field of research in cancer biology and therapeutics. One such opportunity in cellular immunotherapy is adoptive cell transfers. With the recent approval of CAR-T therapy as a cancer treatment, a whole new paradigm of cancer treatment has opened-up, with a ray of hope for relapsed/refractory cancer patients. Despite promising clinical outcomes, the therapy is in its early phase and remains out of reach for most patients due to its high cost and logistic challenges. In India, these therapies are unavailable and further confounded by the economic challenges and a large population. In this review, we discuss various aspects of T-cell immunotherapies with a special focus on CAR-T in the Indian scenario. We touch upon the basic scientific aspects, mechanism of action, manufacturing, clinical aspects and commercial aspects of the CAR-Tcell therapies and its future worldwide and in India.

Information-sharing experiences of professionals looking after children with cancer: a qualitative exploration from a specialist paediatric oncology unit in India.

Background: Childhood cancer often involves a long-term engagement of children and their parents with health services. During this journey, communications between professionals, parents and young people can be stressful for all the stakeholders. This study explores the communication preferences in paediatric oncology. Objectives: The objective of the present exploratory qualitative study was to understand the views of professionals regarding information exchange during cancer treatment of children and complement these findings with clinic-based ethnographic observation of real-life consultations. Methods: Using qualitative methods, in-depth interviews were conducted with paediatric oncology professionals. The interviews had been audio-recorded and transcribed verbatim. Alongside in-depth interviews, real-life interactions between parents, professionals and children were observed. Data were analysed using a thematic analysis framework as suggested by Braun and Clark. Results: Paediatric oncology professionals (n = 14) were interviewed from diverse professional backgrounds that included consultant paediatric oncologists, junior specialist trainees in paediatric oncology, paediatric oncology nurses, social workers, survivor counsellor and psychologists looking after children with cancer. Additionally, clinic-based ethnographic observations (n = 10) of interactions between professionals, parents and young people were also conducted. The following themes emerged from the interviews: a) Information needs of children were very different from adolescents. Children were more worried about 'here and now'; b) adolescents were, on the other hand, mostly worried about the 'impact of cancer on their broader life, friendships and academics'; c) parents were curious about the outcome, costs and effectiveness of treatment, and different patterns emerged for mothers and fathers; d) information needs were dynamic and different at the start of the treatment, during treatment, at remission or end of life; e) the journey of the clinicians themselves impacted information-sharing practices; and f) direct observation of consultations highlighted the importance of priming parents before delivery of information, having multiple family members during the conversation and managing intense emotions expressed during the session. Conclusion: Paediatric oncology professionals need to be sensitive about the dynamic nature of information needs while interacting with children and parents of children with cancer. The above findings may help tailor the discussions that professionals ought to have with families with a child with cancer. The results may contribute to the understanding as well as to developing training courses on communications in paediatric oncology for low- and middle-income countries.

Germline Biallelic Mismatch Repair Deficiency in Childhood Glioblastoma and Implications for Clinical Management.

We report a case of a 9-year-old boy with glioblastoma with a past history of colon cancer. Germline bi-allelic DNA-mismatch repair deficiency was diagnosed by a lack of immunohistochemical staining for PMS2 in the tumor and normal tissue. Family history was lacking. Sequencing confirmed compound heterozygous PMS2 mutations. A second hit in the DNA-polymerase-ε gene led to complete DNA-replication repair deficiency. This contributed to an ultra-hypermutated phenotype. Temozolomide was excluded from the treatment. PD-1 immunotherapy at recurrence contributed to extending post-relapse survival up to 11 months. Challenges included managing initial immune "flare" related to "pseudo-progression" and access to drug. Family screening diagnosed the sibling with Lynch syndrome. This is the first report of a child with a brain tumor treated with immunotherapy from India. Our report supports the routine inclusion of immunohistochemistry for mismatch repair proteins in the evaluation of pediatric high-grade glioma as this may directly impact the clinical care of these children and families.