SINCE the discovery of dendritic cells by Dr Ralph Steinman in 1973, much research has been carried out to elucidate the basic functional mechanism of dendritic cells.
Many medical research institutes and universities have conducted research in the use of dendritic cells in anti-cancer immunotherapy.
The ability of dendritic cells to enable selective and effective attack against tumour cells by T cells gave rise to great hopes that it would be an ideal cancer treatment.
Dr Hasumi is the man behind the the Human Initiated Therapeutic Vaccine therapy. His current protocol involves intra-tumoural injection (injecting directly into the tumour) of immature autologous (from the patient’s own body) dendritic cells in combination with tomotherapy (a type of radiation therapy).
Since 2008, over 360 late stage cancer patients have received this therapy in his Tokyo clinic and a remarkably high complete/partial recovery rate has been noted. His most recent results involving 26 patients with advanced treatment refractory cancer were published in the April edition of the journal,
Cancers.
In summary, he has shown that combining immunotherapy with radiation therapy successfully eliminated metastatic and recurrent tumours on initial treatment in 21 of the 26 patients, with 13 of the 26 having no evidence of recurrent disease when evaluated by CT scans at various intervals of follow-up.
The overall disease-free period of the responding patients at the current time stands at about a year.
New startegies for cancer treatment
There are currently a few new directions that are being pursued in cancer therapy. They include:
Strategy 1: Remove the tumour’s mask. Cancer cells hide within normal structures like blood vessels. In order to conceal themselves, cancer cells rely on proteins from nearby healthy cells to hide their malignant proteins. New agents such as engineered peptide antibodies are increasingly able to strip away these disguises, exposing the tumours.
Strategy 2: Make the tumour less productive. Cancer cells actively pump out factors called immune system suppressors that wave off immune sentries and mislead them into thinking that the tumours are normal, healthy cells.
New compounds currently being tested can suppress the suppressors. Cancers are also rich in suppressor T cells, which direct the natural killer cells not to attack the cancer cells, resulting in immune tolerance. Drugs and radiation can wipe out these suppressor T cells and break the immune tolerance.
Strategy 3: Stack the immune system’s deck. The body’s T cells, which target invaders, may not be able to recognise the cancer cells. However, it is now possible to take from a patient some mononuclear cells and induce them to differentiate into immature dendritic cells (or antigen presenting cells).
When mixed with cancer cells, the dendritic cells will identify the cancer cell proteins and pass the information to cytotoxic T lymphocytes (natural killer T cells), thereby training the infantry T cells to spot the bad guys. The killer T cell population can also be enhanced in the lab and then injected back into the body.
Strategy 4: Build the right immune cells. Another way to sensitise T cells to detect cancer cells is to redesign them for the job. Scientists do this by extracting the cells, genetically modifying them to recognise tell-tale cancer proteins, and then using these supercells to treat the patient.
The HITV protocol
Dr Hasumi’s HITV protocol is basically Strategies 2 and 3 in combination with conventional radiotherapy.
This patient-specific induced therapeutic cancer vaccine is believed to be effective in killing off microscopic and tiny nests of cancer cells, thereby preventing any future cancer recurrence.
There are three essential steps:
1. Firstly, the intra-tumoural injection of immature dendritic cells, followed by infusion of cytokine induced natural killer cells results in millions of cytotoxic T cells which have been trained to zero in on the cancer cells.
The direct injection of immature dendritic cells into the tumour allows for adequate numbers of dendritic cells to reach the tumour site. The dendritic cells also have the benefit of an ideal in vivo environment in the patient’s body and there is less chance of antigenic difference.
2. This is followed by radiotherapy a week later, which causes further DNA damage, protein damage and apoptosis of the cancer cells, resulting in debulking of the tumour.
Radiotherapy also wipes out the regulatory T cells, thereby helping to break up the cancer’s immune tolerance.
Combination with radiotherapy achieves two goals – damaging the cancer cells to kill them and to expose their DNA and proteins, and wiping out the regulatory T cells within the tumours.
3. A second intra-tumoural injection of immature dendritic cells, followed by cytotoxic T cells infusion, allows the immune system to mop up all remaining cancer cells, including those which could have undergone transformation or mutation.
This second round of HITV treatment aims to wipe out newly mutated cancer cells.
HITV therapy has been found to be highly effective in the following patient conditions:
1. Solid tumours
HITV is applicable for any type of solid cancers and any stage. However it is not suitable for haematopoietic cancers such as leukaemia.
2. Tumours are localised in treatable sites
As intra-tumoural injection of dendritic cells is the hallmark of HITV, it is important that the tumour is located in sites which are accessible by needle.
3. Tumour size of less than 3cm in diameter
This limitation is due to the standard beam diameter of tomotherapy, which is 3cm. Dendritic cell vaccine is also ineffective when injected into the necrotic centre of large tumours.
4. Less than five metastatic tumour lesions
Again, the limitation is due to the adverse reactions to radiotherapy that may occur when multiple sites have to be treated in one sitting. However, Dr Hasumi has experience in treating up to 15 lesions in one go.
5. No pleural or ascitic effusion
Pleural and ascitic effusion are typical signs of extensive cancer dissemination and the chances of success in such cases is greatly diminished.
He’s in town
Dr Kenichiro Hasumi will be in Kuala Lumpur on Oct 24 to deliver a lecture entitled “Breakthrough in Cancer Treatment – The Cure to Cancer Is Now In Malaysia”. The lecture will be held at the Le Meridien Hotel, Kuala Lumpur, at 7.30pm. For enquiries, call 03 7784 6686.
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