Background Very few cancer patients were enrolled in COVID-19 vaccine studies. In order to address this gap of knowledge, real world studies are mandatory. Aim of this study was to assess both humoral and cellular response after a mRNA vaccination schedule. Patients and methods Eighty-eight consecutive cancer patients treated with PD-1/PD-L1 inhibitors were enrolled from the beginning of the vaccination campaign for frail patients. Blood samples for humoral and cell-mediated immune response evaluation were obtained before vaccination (T0), before the second administration (T1) and 21 days after the second dose (T2). The primary end-point was the evaluation of the percentage of participants showing a significant increase in SARS-CoV-2 specific T cells, measured by an ELISPOT assay, after the second dose of BNT162b2 vaccine. The proportion of patients who reached the primary endpoint is computed together with its exact binomial 95% confidence interval (95%CI). Results In SARS-CoV-2 naïve subjects, Spike-specific T-cell response was almost undetectable at T0 (median 0.0 IFNγ SFU/million PBMC IQR 0-7.5) and significantly increased at T1 and T2 (median 15.0 IFNγ SFU/million PBMC 25th-75th 0-40 vs 90 IFNγ SFU/million PBMC 25th-75th 32.5-224; respectively) (p<0.001). Focusing on naïve and experienced SARS-CoV-2 subjects no differences were reported both in terms of CD4 and CD8-specific T-cell response, suggesting that BNT162b2 is able to elicit both adaptive responses after complete vaccination schedule, regardless previous SARS-CoV-2 exposure. The level of SARS-CoV-2 NT Abs was low at T1 in SARS-CoV-2 naïve subjects [median 1:5 (IQR 1:5-1:20)] but reached a significantly higher median 1:80 (25th-75th 1:20-1:160) at T2 (p<0.0001). Moreover no COVID-19 cases were documented throughout the period of study. Conclusions Our data have demonstrated that the administration of a full course of BNT162b2 vaccine elicited a sustained immune response against SARS-CoV-2 regardless to the type of cancer and/or the type of ICIs.

Background The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti PD-1/PD-L1 with or without chemotherapy six months after BNT162b2 vaccine. Patients and methods In the previous study, 88 patients were enrolled, while the analyses below refer to the 60 patients still on immunotherapy at the time of the follow up. According to previous SARS-CoV-2 exposure, patients were classified in SARS-CoV-2 naïve (without previous SARS-CoV-2 exposure) and SARS-CoV-2 experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Abs) titer against B.1.1 strain and total anti-Spike IgG concentration were quantified in serum samples. ELISpot assay was used for quantification of anti-Spike interferon gamma (IFNγ) producing cells/10 6 peripheral blood mononuclear cells (PBMC). Fifty patients (83.0%) were on immunotherapy alone, while ten patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. Results Median T-cell response at six months was significantly lower than that measured at three weeks after vaccination (50 interquartile range (IQR) 20-118.8 vs 175IQR 67.5-371.3 IFNγ producing cells/10 6 PBMC;p<0.0001). The median reduction of IgG concentration was 88% in SARS-CoV-2 naïve subject, 2.1% in SARS-CoV-2 experienced subjects. SARS-CoV-2 NT Abs titer was stable maintained in SARS-CoV-2 experienced subjects while a significant decrease was observed in SARS-CoV-2 naïve subjects (from median 1:160 IQR 1:40-1:640 to median 1:20 IQR 1:10-1:40;p<0.0001). A weak correlation was observed between SARS-CoV-2 NT Abs and Spike-specific IFNγ producing cells at both six months and three weeks after vaccination (r=0.467;p=0.0002 and r=0.428;p=0.0006,respectively). Conclusions Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2 naïve subjects. Our data support administering third dose of COVID-19 vaccine to cancer patients treated with PD1/PD-L1 inhibitors.

In the past years cancer treatments have drastically changed, mainly due to the development of immune checkpoint inhibitors capable of immune modulation in vivo, thus providing major clinical benefit in a number of malignancies. Simultaneously, considerable technical refinements have opened new prospects for the development of immune cell-based medicinal products and unprecedented success with chimeric antigen receptor (CAR)-T cells targeting B-cell hematologic malignancies has been obtained. However, T cell therapies introduced and performed in the field of solid tumors have produced so far only limited responses in selected patient populations. This standstill is attributable to the difficulty in identifying target antigens which are homogeneously expressed by all tumor cells while absent from normal tissues, and the limited T cell persistence and proliferation in a hostile tumor microenvironment that favors immune escape. Replicating the results observed in hematology is a major scientific challenge in solid tumors, and ongoing translational and clinical research is focused on obtaining insight into the mechanisms of tumor recognition and evasion, and how to improve the efficacy of cellular therapies, also combining them with immune checkpoint inhibitors or other agents targeting either the cancer cell or the tumor environment. This paper provides an overview of current adaptive T cell therapy approaches in solid tumors, the research performed to increase their efficacy and safety, and results from ongoing clinical trials.