Clinical Immunotherapy for Cancer and Innovative Therapies

The mission is to personalise treatment through the application of translational medicine for the development of new anti-cancer drugs and new immunotherapy approaches in patients with solid tumours. This is achieved through close collaboration with the preclinical sector, with the aim of rapidly translating knowledge gained in the laboratory to the patient’s bedside. These new approaches are also integrated with the study of the genetic and phenotypic characteristics not only of the tumour but also of the tumour microenvironment.

The clinical work of the Medical Oncology Unit is carried out through both inpatient and outpatient services.  

The Department has 4 inpatient beds located on the 8th floor, Block F, staffed by 2 senior consultants and a medical oncology trainee. The ward admits patients undergoing conventional-dose and high-dose chemotherapy with autologous circulating haematopoietic stem cell transplantation, patients with solid tumours of various origins enrolled in Phase I clinical trials (primarily involving new immunomodulatory drugs or drug combinations), and patients enrolled in clinical trials who experience side effects resulting from treatment with experimental drugs.  

Outpatient care is provided within the Phase I Clinical Trials Group of Medical Oncology 1 (coordinated by Prof. F. de Braud), involving the assessment and recruitment (initial consultations) of patients who may be eligible for innovative trials involving experimental drugs.

Transplantation activities are primarily aimed at patients with poor-prognosis testicular germ cell tumours who have relapsed following first-line chemotherapy (in collaboration with the Urology Department; the international TIGER study sponsored by the EORTC) and poor-prognosis sarcomas (in collaboration with the Medical Oncology 2 Department).  

In 2021, the Unit obtained Joint Accreditation Committee ISCT-Europe & EBMT (JACIE) accreditation and, in 2022, accreditation from the National Transplant Centre (CNT) to perform autologous transplants for solid tumours as part of the Transplant Programme of the National Cancer Institute of Milan.

The SS carries out its specific activities in accordance with internal quality protocols, which are reviewed and updated periodically. 

In terms of clinical research, the Department is part of the OM1 Phase I Study Group, which conducts Phase I/Ib clinical trials in solid tumours. These trials test drugs with innovative mechanisms of action or drug combinations, particularly those with immunomodulatory activity. Trials involving first-in-human drugs are also conducted. Dr Di Nicola is the Principal Investigator (PI) and co-investigator of approximately 20 and 40 Phase 1/1b studies, respectively.

The Unit has a preclinical research laboratory staffed by two biologists, a biotechnologist and one student per year from the Master’s Degree Course in Biotechnology, working on their thesis in collaboration with the units of the Department of Experimental Oncology.  

The research activities of the SS are carried out both in the preclinical setting, aimed at optimising innovative therapeutic strategies, and within the context of spontaneous clinical trials and/or those sponsored by pharmaceutical companies involving innovative drugs.    

The main areas of preclinical research are:

1. Establishment of a bank for the collection of peripheral blood and tissue samples from all patients undergoing phase 1–2 immunotherapy treatments (in particular those involving combinations of immune checkpoint inhibitors) to identify new prognostic factors and predictors of response (INT 151/15 Study).

2. Evaluation of the role of the extracellular matrix in inducing an immunosuppressive tumour microenvironment that leads to a poor response to immunotherapy with immune checkpoint inhibitors.  

3. Development and application of adoptive immunotherapy. This line of research comprises two main strands:  

a) Engineering of T lymphocytes (CAR-T cells) through the expression of single-chain antibody variable fragments (ScFvs) capable of recognising tumour antigens in an HLA-independent manner (the “FORCE4CURE” project in collaboration with four IRCCS centres in Lombardy; Targeted Research Line 2);

b) Optimisation of the selection, expansion and reinfusion processes of autologous anti-tumour lymphocyte populations from peripheral blood for the development of an effective adoptive immunotherapy programme in patients with solid tumours (Targeted Research Line 2).

4. Analysis of epigenetic events involved in CAR T-cell maturation: new therapeutic combinations for solid tumours (Current Research Line 2).