**Acknowledgements**

This study was supported by grants-in-aid from the Ministry of Health, Labor, and Welfare, Japan.

## **Conflict of interest**

Dr. Fujimoto received consultancy fees from Boehringer Ingelheim, Ono, Bristol-Myers Squibb, Kyorin, and Kissei. Dr. Fujimoto also received honoraria or research funding from Hisamitsu, Chugai, Ono, Taiho, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, GlaxoSmithKline, and MSD.

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**Author details**

Asako Matsuda and Nobukazu Fujimoto\*

provided the original work is properly cited.

\*Address all correspondence to: nobufujimot@gmail.com

Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Immunotherapy in Malignant Pleural Mesothelioma DOI: http://dx.doi.org/10.5772/intechopen.95823*

*Immunotherapy in Malignant Pleural Mesothelioma DOI: http://dx.doi.org/10.5772/intechopen.95823*

*Advances in Precision Medicine Oncology*

including MPM.

**9. Conclusion**

cellular therapy.

**Acknowledgements**

and Welfare, Japan.

**Conflict of interest**

therapy after chemotherapy (DENIM trial) [34].

**8. Chimeric antigen receptor T-cell therapy**

were treated with DC vaccinations (autologous DCs pulsed with tumor lysate from five mesothelioma cell lines). Of these, two patients experienced a partial response and all nine patients established disease control. The median OS was longer than 22.8 months. Based on those promising results, an ongoing phase II/III study is currently testing DCs loaded with allogeneic tumor cell lysate as a maintenance

Chimeric antigen receptor (CAR) T-cells can be used to target specific tumor antigens directly. CAR T-cell therapy has shown clinical efficacy for hematological malignancies, and it was approved by the United States Food and Drug Administration for B cell acute leukemia and diffuse large B-cell lymphoma. Several clinical trials are ongoing to test CAR T-cell therapy on both hematological malignancies and solid tumors [35]. CAR T-cells that targeted WT-1, fibroblast activation protein (FAP), or mesothelin (MSLN) were tested in a clinical trial on MPM. Hass et al. reported the results of a clinical trial for testing CAR T-cells that targeted MSLN on 15 patients with MPM. The CAR T-cells were applied as a monotherapy or in combination with low-dose cyclophosphamide, for solid tumors [36]. The best overall response was stable disease (11 of 15 patients). Currently, several phase I trials are ongoing to examine the efficacy of CAR T-cell therapy in solid tumors,

The prognosis of MPM remains poor. A PD-1/PD-L1 blockade is an effective treatment option for MPM. The combination of nivolumab (anti-PD-1 antibody) and ipilimumab (anti-CTLA-4 antibody) could be a standard first-line treatment. Additionally, the combination of an ICI with conventional chemotherapy might be a promising treatment option. Cellular therapies and cancer vaccines must overcome many challenges, such as T-cell migration to the tumor and infiltration into the tumor. Improvements in cancer therapies are urgently needed to overcome these difficulties. Further research with large-scale clinical trials are needed to clarify the utility and safety of these immunotherapies in MPM. In addition, in this new era of precision medicine, we need to develop biomarkers to identify which patients would benefit from ICI-ICI combinations, ICI plus chemotherapy, or

This study was supported by grants-in-aid from the Ministry of Health, Labor,

Dr. Fujimoto received consultancy fees from Boehringer Ingelheim, Ono, Bristol-Myers Squibb, Kyorin, and Kissei. Dr. Fujimoto also received honoraria or research funding from Hisamitsu, Chugai, Ono, Taiho, Boehringer Ingelheim,

Bristol-Myers Squibb, Novartis, GlaxoSmithKline, and MSD.

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