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**Chapter 5**

**Provisional chapter**

**Gene-based Interventions for Cancer Immunotherapy**

Immunotherapy of cancer has deservedly gained much attention in the past few years and is likely to continue to advance and become a fundamental cancer treatment. While vaccines, chimeric antigen receptor (CAR) T cells and checkpoint blockade have received the lion's share of the attention, an important direct role for gene transfer as an immunotherapy is emerging. For example, oncolytic viruses induce immunogenic cell death, thus liberating both antigens and the signals that are necessary for the activation of antigenpresenting cells, ensuring stimulation of an adaptive response. In another example, transfer of prodrug converting enzymes, such as the herpes simplex virus-thymidine kinase (HSV-tk) gene or the cytosine deaminase gene, has been shown to promote an immune response, thus functioning as immunotherapies. Alternatively, our own work involves the use of nonreplicating viral vectors for the simultaneous delivery of gene combinations that promote both cell death and an immune response. In fact, our gene transfer approach has been applied as a vaccine, immunotherapy or *in situ* gene therapy, resulting in immunogenic cell death and the induction of a protective immune response. Here, we highlight the development of these approaches both in terms of technical advances

**Keywords:** vaccine, CAR-T cell, oncolytic virotherapy, suicide gene, viral vectors

**Gene-based Interventions for Cancer Immunotherapy**

© 2016 The Author(s). Licensee InTech. 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, provided the original work is properly cited.

© 2018 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, provided the original work is properly cited.

DOI: 10.5772/intechopen.80386

Otto L.D. Cerqueira,

Otto L.D. Cerqueira,

Paulo Roberto Del Valle,

and Bryan E. Strauss

**Abstract**

and clinical experience.

Gissele Rolemberg Oliveira Silva,

Gissele Rolemberg Oliveira Silva,

http://dx.doi.org/10.5772/intechopen.80386

Igor de Luna Vieira, Marlous Vinícius Gomes Lana,

Igor de Luna Vieira, Marlous Vinícius Gomes Lana, Nadine Gimenez, Otavio Augusto Rodrigues,

Paulo Roberto Del Valle, Samir Andrade Mendonça

Nadine Gimenez, Otavio Augusto Rodrigues,

Samir Andrade Mendonça and Bryan E. Strauss

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

#### **Gene-based Interventions for Cancer Immunotherapy Gene-based Interventions for Cancer Immunotherapy**

DOI: 10.5772/intechopen.80386

Otto L.D. Cerqueira, Gissele Rolemberg Oliveira Silva, Igor de Luna Vieira, Marlous Vinícius Gomes Lana, Nadine Gimenez, Otavio Augusto Rodrigues, Paulo Roberto Del Valle, Samir Andrade Mendonça and Bryan E. Strauss Otto L.D. Cerqueira, Gissele Rolemberg Oliveira Silva, Igor de Luna Vieira, Marlous Vinícius Gomes Lana, Nadine Gimenez, Otavio Augusto Rodrigues, Paulo Roberto Del Valle, Samir Andrade Mendonça and Bryan E. Strauss

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80386

#### **Abstract**

Immunotherapy of cancer has deservedly gained much attention in the past few years and is likely to continue to advance and become a fundamental cancer treatment. While vaccines, chimeric antigen receptor (CAR) T cells and checkpoint blockade have received the lion's share of the attention, an important direct role for gene transfer as an immunotherapy is emerging. For example, oncolytic viruses induce immunogenic cell death, thus liberating both antigens and the signals that are necessary for the activation of antigenpresenting cells, ensuring stimulation of an adaptive response. In another example, transfer of prodrug converting enzymes, such as the herpes simplex virus-thymidine kinase (HSV-tk) gene or the cytosine deaminase gene, has been shown to promote an immune response, thus functioning as immunotherapies. Alternatively, our own work involves the use of nonreplicating viral vectors for the simultaneous delivery of gene combinations that promote both cell death and an immune response. In fact, our gene transfer approach has been applied as a vaccine, immunotherapy or *in situ* gene therapy, resulting in immunogenic cell death and the induction of a protective immune response. Here, we highlight the development of these approaches both in terms of technical advances and clinical experience.

**Keywords:** vaccine, CAR-T cell, oncolytic virotherapy, suicide gene, viral vectors

© 2016 The Author(s). Licensee InTech. 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, provided the original work is properly cited. © 2018 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, provided the original work is properly cited.
