Cancer Immunotherapy

Immunotherapy, a type of cancer treatment designed to eradicate disseminated cancer by harnessing the potential of the immune system. Immunotherapy agents do not directly attack the tumour but instead mobilize the immune system -this can be achieved through various approaches that utilize adaptive or innate immunity.

Historically, the mainstays of cancer treatment has largely relied on killing tumor cells with surgery,chemotherapy and radiotherapy. But these methods have limitations including severe systemic toxicities, bystander effects on normal cells, etc.

The critical relationship between immune function and cancer was first proposed by Rudolf Virchow 150 years ago when he observed the prevalence of leukocytes in tumours. For the next 100 years, there was little clinical demonstration that the immune system could be mobilized to provide a reproducible benefit for patients with cancer. Since the regulatory approval of ipilimumab in 2011, the field of cancer immunotherapy has been experiencing a renaissance. Immunotherapy has become an important part of treating some types of cancer owing to its unique science and its potential for substantial and long-term clinical benefit.

The main types of immunotherapy can be broadly subdivided into non-antigen-specific and antigen-specific categories. Non-antigen-specific strategies include nonspecific immune stimulation and Immune checkpoint inhibitors, whereas antigen-specific strategies include adoptive cell transfer of autologous cancer-specific T cells and various therapeutic vaccination approaches.

Immune checkpoint inhibitors

Immune checkpoints are proteins in the immune system that either turn up a signal or turn down a signal. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells are able to kill cancer cells better.

Examples of immune checkpoint proteins (targets) found on T cells or cancer cells include:

Nonspecific immune stimulation

Nonspecific immune stimulation can be achieved with agents that stimulate immune effector cells such as T cells and APCs(for example, DCs), or inhibit and/or deplete immunoregulatory cells such as TReg cells.

Effector T cells can be stimulated withcytokines such as IL-2 and IFNα.Cytokine immunotherapy with IL-2 or IL-12 can lead to rejection of experimental tumors partially through an NKG2D-dependent mechanism that likely includes NK and T-cells. Approaches that aim to provide full APC activation use adjuvants such as TLR ligands.

TReg cells can be depleted by targeting the IL-2 receptor with the anti-CD25 (IL-2 receptor α-chain) antibody daclizumab, the recombinant IL-2–diphtheria toxin conjugate denileukin diftitox or low-dose treatment with the chemotherapeutic cyclophosphamide.

Examples of Nonspecific immune stimulation proteins (targets) found on T cells or cancer cells include: