Immunotherapy is a type of cancer treatment that boosts the body's natural defenses to fight cancer. There are several types of immunotherapy including cancer vaccines, T cell therapy, oncolytic virus therapy, non-specific immunotherapies, and monoclonal antibodies. T cell therapy involves modifying a patient's T cells to recognize and destroy cancer cells, while oncolytic virus therapy uses genetically modified viruses to kill cancer cells. Immunotherapies have shown promise in treating various forms of cancer, but greater understanding is still needed of how the immune system interacts with tumor cells and the mechanisms by which tumors evade immunity.

1. IMMUNOTHERAPEUTICS
INTRODUCTION: Immunotherapy is the treatment of disease by activating or suppressing the immune system.
Immunotherapies designed to elicit or amplify an immune responses are classified as activation immunotherapies are
classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression
immunotherapies.
The term immunity is derived from Latin word “immunis” which means exempt. The cells and
molecules responsible for immunity constitute the immune system and their collective and coordinated response to
foreign substances is called the immune response.
In recent years, immunotherapy has become of great interest to researchers, clinicians and
pharmaceutical companies particularly in its promise to treat various forms of cancer. Cell based immunotherapies
are effective for some cancer. Immune effector cells such as lymphocytes,macrophages, dendritic cells, Natural killer
cells, cytotoxic T lymphocytes etc. Immunomodulators are the active agents of immunotherapy. They are a diverse
array of recombinant, synthetic and natural preparations.
Immunotherapy also called as Biologic therapy is a type of cancer treatment that boosts the body
natural defenses to fight cancer. Substances made by the body or in a laboratory to improve or restore immune system
function are used. Immunotherapy may work by;
 Stopping or slowing the growth of cancer cells.
 Stopping cancer from spreading to other parts of the body.
 Helping the immune systemwork better at destroying cancer cells.
There are several types of immunotherapy. They are as follows:-
 Monoclonal antibodies and Tumor agnostic therapies
 Non- specific immunotherapies
 Oncolytic virus therapy
 T cell therapy
 Cancer vaccines.
Explanation:
1. Cancer vaccines: A cancer vaccine is another method used to help the body fight disease. A vaccine
exposes the immune systemto an antigen which triggers the immune systemto recognize and destroy that
antigen or related materials. Two types of cancer vaccines are there – Treatment vaccines and prevention
vaccines.
2. T cell therapy: T cells are immune cells that fight infection. At the same time same T –cells are removed
from a patient’s blood and changed in the laboratory so they have specific proteins called receptors. The
receptors allow those T –cells to recognize the cancer cells. The changed T-cells are grown in the laboratory
and returned to the patient’s body. Once in the body, they seek out and destroy cancer cells. This type of
therapy is called chimeric antigen receptor (CAR) T cell therapy.
3. Oncolytic virus therapy: Oncolytic virus therapy uses genetically modified viruses to kill cancer cells.
The doctor first injects a virus into the tumor where the virus then enters the cancer cells and makes copies
of itself. Thus the cell bursts and die releasing specific substances called antigens thus triggering the patient’s
immune systemto target all the cancer cells in the body and that have those same antigens. The virus does
not enter the healthy cells.
The first Oncolytic virus therapy to treat melanoma was talimogene laherparepvec (lmlygic) or
T-VEC. The virus is genetically modified version of the herpes simplex virus that causes cold sores.

2. 4. Non- specific immunotherapies: Most non-specific immunotherapies also help the immune system
destroy cancercells and given after or at the same time as othercancer treatments. Two common non-specific
immunotherapies are Interferon and Interleukins where interferon help the immune system fight cancer
and may slow the growth of cancer cells and interleukin help the immune systemproduce cells that destroy
cancer. An interleukin made in the laboratory is called Interleuukin-2 or aldesleukin.
5. Monoclonal antibody: When the body’s immune system detects something harmful it produces
antibodies where antibodies are proteins that fight infections. Monoclonalantibody can be used as a targeted
therapy to block an abnormal protein in cancer cell.
A tumor marker may be produced by the tumor cells in order to detect the presence of cancer based on the
measurement in body fluids and tissues.The search for tumor marker gene goes back to the discovery of Bence
Jones protein, a light chain immunoglobulin found in patients with multiple myeloma.
HUMANIZATION ANTIBODY THERAPY: Humanization (also called reshaping or CDR grafting) is now a
well-established technique for reducing the immunogenicity of monoclonal antibody from xenogeneic sources
and for their activation of the human immune system.
Humanized antibodies are antibodies from non- human species whose protein sequences have been
modified to increase their similarity to antibody variants produced naturally in humans. The process of
humanization is usually applied to monoclonal antibodies developed for administration to humans e.g. antibodies
developed as anti- cancer drugs. Humanization can be necessary when the process of developing a specific
antibody involves generation in a non-human system. The protein sequence of antibodies produced in this way
are partially distinct from homologous antibodies occurring naturally in humans, and therefore partially
immunogenic when administered to human patients.
Production of humanized antibodies: In order to humanize an antibody the design of the humanized
antibody is the critical step in reproducing the function of the original molecule. This design includes the extent
of CDRs, the human framework to use and the substitution of residues from the rodent mAb into the human
framework regions (back mutations).
Off late, phage libraries have been used to vary the amino acids at chosen position.Some groups
use variable regions with high amino acid sequence identity to the rodent variable regions; with high amino acid
sequence identity to the rodent variable regions; others use consensus or germ line sequences while still others
select a framework sequences within each light or heavy chain variable region from several different human
mAbs.
USES: 1. It includes reduction in the immunogenicity of an antibody.
2. Therapeutic value of an antibody increases after humanization.
Immunotherapeutics in clinical practice/ Role of immunotherapeutics
 Von Behring and Wernicke found that animals could be cured of diphtheria. An injection of sear
produced by animals immunized with an attenuated form of diphtheria successfully treated a child with
diphtheria.
 Drugs like thalidomide, Lanalidomide, Imiquimod can boost immune response. This promise without
the serious side effects of chemotherapy, radiation therapy and surgery.
 T- lymphocyte associated antigen 4, programmed cell death I and programmed cell death protein ligand
I are the classes ofdrugs based on immunologic manipulation and are collectively known as checkpoint
inhibitors. Checkpoint inhibitors have shown a remarkable antitumor efficacy in a broad spectrum of
malignancies.
 Combination of immunotherapeutics with radiation: Radiation therapy aids immune systemin two ways:
Either via direct toxicity of tumor cells or Radiation works as an immune-adjuvant and the
inflammatory microenvironment leads to induction of immune response.

3. In various tumor cells, experiments have demonstrated clinical
efficacy of combination with IT. CTL-4 blockade showed synergy with RT.
CONCLUSION: Novel developments in immunotherapy have led to a new era for cancer
treatment. Immunotherapeutics specifically PD-1 and anti PD-L1 antagonism have shown
to elicit important, durable and safe responses in many tumor types that were once
considered among the most desperate malignancies.
1. One of the key limitations of achieving broader responses in clinical trials is the
complexity of the host immune system and its interaction with host cells.
2. Besides a more in depth understanding of tumoral antigen production and
recognition as well as of the escape mechanisms from host immunity and the
antitumoral death responses is essential to overcome the major problems of immune
related drug development.
3. Increased efforts in translational research will further shed light on anticancer drug
developments, especially in the immunotherapy area which will lead to a better
understanding of the dynamic interactions between the host and tumor cells.
Among the combination strategies a backbone with either PD-1 or PD-L1
antagonist drugs along with certain cytotoxic chemotherapies radiation, targeted drugs and novel
checkpoint stimulators will be the most promising approaches in future.