Cancer Immunotherapy

Submitted By -Nivedita ShahM.Sc. Biotechnology Part I sem IIBanasthali VidyapithRoll no.- 13937

Introduction Immunotherapy -the most recent advanced

technique in cancer therapy.• Immunotherapy works to harness the innate

powers of the immune system to fight cancer.• It fights cancer more powerfully, to offer long-

term protection, with less side effects.• It may hold greater potential than current

treatments, due to unique properties of Immune System.

Immunotherapy is often characterized as- Active, Passive, or Combinatory.

Cancer Immunotherapy is the use of immune system to reject Cancer. The main purpose premise is stimulating the patient’s immune system to attack the malignant tumour cells that are responsible for the disease.

FIG 1: IMMUNOTHERAPY

History Although cancer immunotherapy is being touted as a recent

breakthrough in cancer treatment, its origins at Memorial Sloan Kettering go back more than a century. In the 1890s, William Coley, a surgeon at New York Cancer Hospital (the predecessor to Memorial Sloan Kettering) discovered cancer patients who suffered from infections after surgery often fared better than those who did not. His finding led to the development of Coley’s toxins, a cocktail of inactive bacteria injected into tumors that occasionally resulted in complete remission. But eventually the use of this treatment fell out of favor.

In the 1960s, research by Memorial Sloan Kettering investigator Lloyd Old led to the discovery of antibody receptors on the surface of cancer cells, which enabled the development of the first cancer vaccines and led to the understanding of how certain white blood cells, known as T cells or T lymphocytes, can be trained to recognize cancer.

Types of Cancer Immunotherapy

Monoclonal Antibodies

Cytokines

Adoptive cell Therapy

Cancer Vaccines

Monoclonal Antibodies Monoclonal antibody(mAbs) therapy, is most widely

used, and a form of Passive Immunotherapy.

•It is a targeted therapy, directed to a single target on a cancer cell, usually an antigen or a receptor site on the cancer cell.

•It binds to Cancer cell-surface specific antigens . When it recognize the antigen against which it is directed, they fit together like two pieces of a puzzle, setting of a cascade of events leading to tumour cell death.Examples: Avastin, Erbitux, Rituxan, Herceptin, Campath, Zevalin, Bexxar etc.

Types of Monoclonal AntibodiesNaked mAbs

Naked mAbs work alone, and are referred to as "naked" because they are unmodified.

Mark targets for immune system - bind to targets and make them more visible. The immune system is triggered and then destroys the target.

Attach to antigens that are responsible for sending important signals that contribute to the target's reproduction.

Binding to cell receptors, so that proteins that trigger growth are blocked. Usually used in cancer treatments.

Conjugated mAbs Conjugated mAbs are

modified with additional material.

Radio immunotherapy (RIT) - These mAbs have radioactive particles directly attached, and deliver them directly to cancerous cells to kill them.

Chemolabeled - These mAbs have a chemotherapy drug attached to their structures, which would normally be too powerful if delivered by itself. This drug kills the cancerous cell.

Cytokines[Active Immunotherapy]•Cytokines are a large group of proteins, that function as short range mediators involved in essentially all biological processes.•Cytokines serve as molecular messengers between cells.•They have important rate-limiting signals.•These are chemically made by some immune system cells.•They are injected, either under the skin, into a muscle, or into a vein.

Most common Cytokines areInterleukins

They act as chemical signals between white blood cells.

Interlukin-2(IL-2) help immune system cells grow and divide more quickly.

A man-made version of IL-2 is approved to treat advanced kidney cancer and metastatic melanoma.

IL-2 can be used as a single treatment for cancer, or can be combined with chemotherapy or with other cytokines such as Interferon-α

Interferons These interferon (IFN) are

chemicals, helping body to resist virus infection and cancer.

Types of (IFN) are:1. IFN-α, 2. IFN-β, 3. IFN-γ

Only INF- α is used to treat cancer.

It is used to treat these cancers:Hairy cell leukemia, Chronic myeloid leukemia, Follicula non-hodgkin’s lymphoma, cutaneous t-cell lymphoma, kidney cancer, melanoma, kaposi Sarcoma.

How does IFN-α therapy works??

Adoptive Cell Therapy•Adoptive cell transfer (ACT) is the transfer of cells into a patient; as a form of cancer immunotherapy. •It requires the generation of highly avoiding tumour-antigen-reactive-T cells.•The cells are most commonly derived from the immune system, with the goal of transferring improved immune functionality and characteristics along with the cells back to the patient.•Interleukin-2 is normally added to the extracted T cells to boost their effectiveness, but in high doses it can have a toxic effect.•The reduced number of injected T cells is accompanied by reduced IL-2, thereby reducing side effects.

ADOPTIVE CELL THERAPY

Cancer Vaccines Unlike other

vaccines, which defends the immune system from germs, Cancer vaccines make person’s immune system attack cancer cells.

There are two Broad Types of Cancer Vaccines

1. Preventive Vaccines:which are intended to prevent

cancer from developing in healthy people.

2. Treatment Vaccines:which are intended to treat an

existing cancer by strengthening the body’s natural defines against the cancer.

Cancer preventive vaccines target infectious agent that cause or contribute to the development of cancer.

Limitations of Immunotherapy1. Many mAbs are not administered as first-line therapy:

mAbs are usually administered as a second, third, or last resort cancer treatment when the immune system is already weakened by chemotherapy, surgery and radiation. This may limit their effectiveness.

2. Not all antigens are the same: All cancers may "look" the same, but they are not. Not all patients' cancers may express the antigen against which a specific monoclonal antibody is targeted. In general, response rates to these "targeted therapies" appear to be around 20 to 30 percent. To optimize this type of therapy, it will be necessary to identify each subgroup of patients with a specific cancer and develop therapies targeted to, or directed specifically at, their individual cancers.

3. Tumour cells mutate: as a result of chemotherapy and radiation treatment, and therefore the target antigen on the tumour cell at which the therapy is aimed also can be changed. If the target changes, then the mAbs, which target those specific antigens, could become ineffective.

4. Toxicity: associated with some targeted therapies can be significant.

Limitations of Adoptive Cell Therapy 1. Not all tumour infiltrating lymphocytes grow well

enough in culture to generate the quantity of cells that would be required to produce a useful anti-tumour effect when they are infused into the patient.

2. Not all tumour infiltrating lymphocytes can be made, in culture, to become more adept at killing the tumour upon return to the patient.

3. Autologous therapy is cumbersome and does not easily lend itself to the commercial scale mass production techniques necessary to reach the multitude of cancer patients world-wide.

Limitations of Cancer Vaccines1. Today, most cancer vaccines are targeted: that means it

made against a specific tumour cell antigenic target. The limitations of targeted vaccines are very similar to the limitations of other targeted change, the target vaccine becomes ineffective.

2. Not all antigen are same3. Autologous vaccine therapy presents many

manufacturing challenges.4. Autologous therapy is costly5. Many cancer vaccines are poorly immunogenic and

require the use of adjuvants to elicit an effective immune response. The addition of adjuvants may increase immunogenicity of vaccine, but may also increase toxicity.

Cancer Immunotherapy Named Science Magazine “Breakthrough of the Year” By Julie Grisham on Monday, December 23, 2013

This image, captured by a scanning electron microscope, shows T cells (orange) attached to a tumor cell. Innovative treatments pioneered by Memorial Sloan Kettering researchers harness the ability of T cells to recognize and destroy cancer cells.