**1. Introduction**

Human body has a natural tendency to fight against diseases including cancer, aided by its immune system. So far, the journey of understanding mechanisms of tumor suppression by immune system and immune suppression by tumor cells, has been overwhelming. The ability of immune cells to differentiate between self and non-self is the key for immune response against cancer cells [1]. However, as cancer cell is actually a transformed self-cell, its ability to escape immune recognition is quite probable and a reason of cancer progression.

The treatment of cancer in the new era has shifted its focus from conventional treatment to physiological treatment, which involves the modification of immune system. This has also led to a concept of personalized treatment where an individual immune system of patient is manipulated rather immune responses obtained based on general population. The efficacy of the immune cells is modified so that its tumor suppression function is improved. This strategy has shown better outcomes and therefore has drawn attention of researchers and clinicians and is now a preferred choice for cancer treatment. The efforts to design universal immune cell-based immunotherapy are also being explored besides personalized immunotherapy [2]. Numbers of approaches have been developed to treat cancer cells using immune-based technology broadly known as cancer immunotherapy (**Figure 1** and **Table 1**).

Among all these immunotherapies, cell-based cancer immunotherapy is getting popular day by day [18–20]. The ability of immune system to inhibit tumor growth and cure it, has been exploited in the development of anti-neoplastic immunotherapy. The immune cells play a key role in adoptive cell therapy (ACT). This is achieved by either expanding the autologous cancer-cognate lymphocytes or empowering them by genetic modifications. These alterations are done *exvivo* and then these cells are infused back to patient to fight against the cancer (**Figure 2**).

Cancer treatments by general immunotherapy have their own limitations due to personal variation in the immune response. In such cases, precision medicine through adoptively modified cellular transfers is being preferred lately. The cells to be transferred may be autologous (self-derived) or allogeneic (donor derived) depending upon the availability. These cells undergo various genetic modifications to suit the cancer types. Allogeneic cells are chosen on the basis of haplo-identical donors, or immune-suppressive conditioning to the patient.

This chapter outlines the emergence and evolvement of ACT, advancements particularly with genetic engineering of autologous cells, treatment approaches, evidences for its effectiveness in refractory patients, and future directions of ACT.

#### **Figure 1.**

*Different approaches to cancer immunotherapy. Arrow indicates different modes through which immunotherapy can be performed. Application of T cells is the foremost choice of the cellular advancement for ACT.*

**121**

**Figure 2.**

*manipulations depending upon cancer types.*

*Advances in Adoptive Cellular Therapy (ACT) DOI: http://dx.doi.org/10.5772/intechopen.95854*

cells

Oncolytic Viruses

Small molecules

**Table 1.**

*Cancer immunotherapy.*

Antibody • Therapeutic use of monoclonal antibodies (mAbs)

• Work like the gene therapy

mRNA), or neoantigens.

induce their activation

*The bullets points highlight their primary modes and mechanisms.*

Vaccine • Meant to treat cancer as a personalized cancer vaccine

vaccines without 'off-target' adverse effects.

• Chemotherapeutics as regulator of immune cells

**Types Salient features Ref.**

• Tumor killing by cytotoxicity; Fc mediated immune effector engagements, non-restricted activation of T-cells and blockade of inhibitory signaling.

• Pro-inflammatory cytokines limit tumor cell growth by stimulating the

Cytokines • Molecular messengers with anti-tumor property, majorly secreted by immune

• Genetically engineered viruses carrying tumor suppressor genes

• When administered, self-replicate in the tumor and induce apoptosis. • Modulate tumor microenvironment and provide anti-cancer immunity

• Helps the patient's immune system for cancer killing and relapses. • May consist of dendritic cells, tumor cell lysate, nucleic acids (DNA and

• Approaches: dendritic cells engineered to express high levels of tumor-associated target antigens, and delivered to relevant lymph nodes to activate T-cells • The DNA and mRNA-based vaccines: taken up by APCs and present to T-cells to

• Tumor neoantigen: tumor specific antigens for the development of cancer

• Indoleamine 2,3-dioxygenase-1 inhibitors boost cellular immunity

*Approach toward adoptive cellular therapy. Cells of interest to perform ACT may be collected through surgery or apheresis. Next, either these cells can be re-infused to patient after its proper expansion or genetic* 

*The salient features with examples of various approaches toward the cancer immunotherapy have been discussed.* 

cytotoxic activity of immune cells against tumor cells. • Recombinant interferon-alpha (IFN-α) and interleukin-2 (IL2) [3–5]

[6]

[7]

[8–15]

[16, 17]

*Advances in Adoptive Cellular Therapy (ACT) DOI: http://dx.doi.org/10.5772/intechopen.95854*

*Advances in Precision Medicine Oncology*

**Table 1**).

(**Figure 2**).

directions of ACT.

immune system of patient is manipulated rather immune responses obtained based on general population. The efficacy of the immune cells is modified so that its tumor suppression function is improved. This strategy has shown better outcomes and therefore has drawn attention of researchers and clinicians and is now a preferred choice for cancer treatment. The efforts to design universal immune cell-based immunotherapy are also being explored besides personalized immunotherapy [2]. Numbers of approaches have been developed to treat cancer cells using immune-based technology broadly known as cancer immunotherapy (**Figure 1** and

Among all these immunotherapies, cell-based cancer immunotherapy is getting popular day by day [18–20]. The ability of immune system to inhibit tumor growth and cure it, has been exploited in the development of anti-neoplastic immunotherapy. The immune cells play a key role in adoptive cell therapy (ACT). This is achieved by either expanding the autologous cancer-cognate lymphocytes or empowering them by genetic modifications. These alterations are done *exvivo* and then these cells are infused back to patient to fight against the cancer

Cancer treatments by general immunotherapy have their own limitations due to personal variation in the immune response. In such cases, precision medicine through adoptively modified cellular transfers is being preferred lately. The cells to be transferred may be autologous (self-derived) or allogeneic (donor derived) depending upon the availability. These cells undergo various genetic modifications to suit the cancer types. Allogeneic cells are chosen on the basis of haplo-identical

This chapter outlines the emergence and evolvement of ACT, advancements particularly with genetic engineering of autologous cells, treatment approaches, evidences for its effectiveness in refractory patients, and future

*Different approaches to cancer immunotherapy. Arrow indicates different modes through which* 

*immunotherapy can be performed. Application of T cells is the foremost choice of the cellular advancement* 

donors, or immune-suppressive conditioning to the patient.

**120**

**Figure 1.**

*for ACT.*


*The bullets points highlight their primary modes and mechanisms.*
