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Dendritic cells prime the immune system to fight infections. – Filepic
Human Initiated Therapeutic Vaccine (HITV) is a form of cancer immunotherapy that is showing some encouraging results.
HOSPITAL Universiti Kebangsaan Malaysia (HUKM) is currently carrying out a small trial utilising a form of immunotherapy called Human Initiated Therapeutic Vaccine (HITV).
In the trial, HITV is used in combination with modulated radiotherapy to treat advanced stage (metastatic) cancers.
HITV is pioneered by Hasumi International Research Foundation’s Dr Kenichiro Hasumi.
It involves the use of dendritic cells to stimulate an immune system response to cancer.
The dendritic cells are harvested from the patient and cultured in a laboratory.
They are then reintroduced back into the patient, along with activated T cells.
Dendritic cells are part of the immune system, and are basically cells that detect foreign or harmful substances.
Upon detection of such potentially harmful cells, other components in the immune system are activated to initiate an appropriate response.
Although there are over 100 types of cancer, they all start with uncontrolled and abnormal cell growth.
Unfortunately, cancer treatment has been slow to develop over the years, especially if compared with other diseases.
But there have been promising developments in recent years.
Different types of therapy
Surgery was the first form of cancer treatment.
In its earliest incarnation, it was a crude and primitive way of dealing with cancer, saddled with many problems and complications.
However, advances in the late 19th and early 20th centuries saw major improvements in treatment outcomes.
Today, surgery continues to be a mainstay of cancer treatment, especially in early-stage cancers.
Chemotherapy refers to the cocktail of drugs used to treat cancer.
Basically, it targets rapidly dividing cells, i.e. cancer cells, interfering with cell division, and ultimately, leading to cell death.
However, this also means that normal cells that rapidly divide, e.g. bone marrow cells, immune cells and hair follicle cells, are also affected. Hence, the often unpleasant side-effects of chemotherapy like nausea, hair loss and vomiting, among others.
One of the most common cancer treatments, radiation therapy, involves targeting high-energy waves at cancer cells to kill them.
Targeted therapy is one of the newer treatment methods, where either drugs or other cancer-killing substances are specifically targeted at cancer cells.
The aim of such treatment is also to avoid killing normal cells.
Stem cell transplants involve the use of stem cells (e.g. bone marrow, peripheral blood stem cells and umbilical cord blood) to treat cancer.
Meanwhile, immunotherapy primes the body’s own immune system to help fight cancer.
Immunotherapy in cancer
The immune system is a biological work of art, comprising many different organs, cells and substances that have specific roles to play in protecting the body against the multitude of assaults it faces daily from different microbes.
Bacteria, viruses and parasites all have certain proteins called antigens on their surfaces.
The immune system detects such antigens, and initiates a series of actions to neutralise such threats.
If the response is inadequate, we fall ill.
Compared to foreign microorganisms, cancer cells are not that different from normal cells, which is why the immune system faces such difficulties identifying them as a threat.
This is why healthy people with normal immune systems can develop cancer.
But what if the immune system could be primed to recognise cancer cells?
Would that enable the body to fight cancer cells on its own?
These are questions researchers have been asking for some time, and have resulted in the field of immunotherapy.
Although relatively new, researchers have made huge strides in this area of cancer therapy.
Here’s a short list of what’s being currently looked at:
- Monoclonal antibodies
These are already being used as part of the treatment for many cancers.
They are designed to recognise and attach to specific antigens on the surface of cells.
There are three main types, which work in differing ways, i.e. triggering the immune system to attack cancer cells, blocking cancer cell division, and carrying drugs or radiation directly to cancer cells to kill them.
- T-cell activation
This type of immunotherapy uses the T cells of the immune system to fight cancer cells.
One example is chimeric antigen receptor (CAR) T-cell therapy.
Here, T cells are extracted and altered with chimeric antigen receptors, which can latch on to the surface of cancer cells.
These are then injected into the body to initiate an immune response against the cancer cells.
Such therapy has shown encouraging results in trials, especially against leukaemias and lymphomas.
- Cancer vaccines
Although not a mainstay of cancer treatment, efforts have been ongoing for decades to develop vaccines for cancer.
While the road has been fraught with difficulties, scientists and researchers are continuing their efforts.
The various types of cancer vaccines in development include:
Tumour cell vaccines - Made from the patient’s own cancer cells, it involves altering the cells and injecting them back into the patient.
The cells are altered to make them more likely to be attacked by the body’s immune system.
Antigen vaccines - These are made using parts of the cancer cells, rather than the whole cancer cell.
Dendritic cell vaccines: Dendri-tic cells essentially function as the immune system’s “spotters”.
They spot cancer cells, then mobilise other types of immune cells to destroy them.
In this vaccine, the patient’s dendritic cells are extracted and exposed to cancer cells in the lab.
They are then injected back into the body to provoke a generalised immune response to the cancer cells.
These vaccines are showing the most promising results when it comes to treatment success.
Sipuleucel-T (Provenge), used for advanced prostate cancer, is an example of a dendritic cell vaccine.
Drugs that target the immune system
Why doesn’t the immune system attack normal cells in the body?
The simple explanation is the presence of “checkpoints” that verify whether cells are native or foreign.
In fact, some cancers are able to circumvent such checkpoints, disguising themselves as natives and thus, avoiding attack from the immune system.
In a similar manner, researchers have developed drugs that use such checkpoints to intensify attacks on cancer cells.
CTLA-4: This checkpoint molecule is found on T cells and can be blocked.
An example of a drug that does this is ipilimumab.
Blocking this checkpoint puts the immune system in heightened readiness, which helps the body attack cancer cells.
Unfortunately, it also exposes normal cells to attack, resulting in serious side effects.
PD-1/PD-L1: There has been some serious buzz on these drugs in recent times.
The PD-1 checkpoint is also found on T cells.
Drugs that target PD-1 or PD-L1, like ipilimumab, also boost the immune system, but for some reason, are more specific and less likely to affect normal cells.
Early clinical trials have found that anti-PD-1 drugs, such as pembrolizumab, shrink advanced melanomas in about 25% of test subjects.
Pembrolizumab was recently approved to treat advanced melanoma, and is being tested against other types of cancer as well.
Nivolumab, another anti-PD-1 drug, has been shown to help with some melanomas, kidney cancers and certain lung cancers.
Larger clinical trials are now underway, both using the drug alone and in combination with other cancer therapies.
HITV in cancer
HITV is actually very similar to dendritic cell vaccines.
The difference is that in HITV, the dendritic cells extracted from the patient are injected directly into the tumour mass, while for dendritic cell vaccines, the dendritic cells undergo tweaks in the laboratory before being injected back into the body.
The trial in HUKM has two arms – one lymphoma and the other, breast cancer – involving about 30 patients.
The lymphoma arm started last year, while the breast cancer component commenced recently.
There are various inclusion and exclusion criteria, but all patients in the trial have one thing in common: they are at the advanced stages of cancer, and have little hope with other treatments.
Basically, the protocol involves the following:
1. Evaluation and extraction of dendritic cells from the patient.
2. Injection of dendritic cells into the patient’s tumours, followed by an injection of activated T cells the next day.
3. Radiation therapy eight to 12 days later.
4. Another course of dendritic cells on day 19 of treatment, followed by an injection of activated T cells the next day.
5. Evaluation of the patient, including progress of treatment, during weeks four to six of treatment.
6. Regular review of patient, with HITV treatment administered when required.
This method of treating cancer has been successfully implemented in Japan by Dr Hasumi.
He has reported very encouraging results, with improved quality and duration of life, especially in view of the fact that the treatment is currently being given to very ill, end-stage cancer patients who would otherwise have no hope of reprieve from other treatments.
The HUKM trial might still be in its infancy, but its results would provide us with more data about the effectiveness of this therapy, and how we can progress from here in the effort to find more effective treatments for cancer.
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