Japanese SearchCareersSitemapContact
Inauguration of Nichi-Asia Life Sciences (in Technical Collaboration with NCRM)

Sunday February 27, 2011

New approach to cancer therapy

A treatment using the body’s own defence cells to fight cancer is now available in Malaysia.

CANCER is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. The cells can spread to other parts of the body through the blood and lymphatic systems.

Despite various advances in medicine, cancer remains a major health problem. It is the second leading cause of death in the world. Cancer research has drastically improved the way cancer is managed today as compared to a decade ago. However the lack of comprehensive understanding of the fundamental principles of cancer initiation and behaviour has severely limited the discoveries of novel diagnostic tools and complete curative therapies.

Globally it is estimated that there are 7.6 million new cancer cases annually, of which 52% occur in developing countries.

The National Cancer Registry reported that 21,773 cancer cases were diagnosed in Peninsular Malaysia in 2006. The age standardised incidence rate (ASR) for all cancers was 131.3 per 100,000. The five most common cancers were breast, colorectal, lung, cervix and nasopharynx. (Adapted from National Cancer Registry, Malaysia, 2006)

Widespread phenomenon

Cancer does not discriminate. It affects individuals from all ages. According to the figures from the National Cancer Registry, the most frequent cancer in children (0-14 years old) was leukemia. In young adults (15-49 years old), the common cancers in men were leukemia nasopharynx, colorectal, lung and brain cancer. While cancers of the breast, cervix, thyroid gland, ovary and colorectal were the more common cancers in women of that age cohort.

Within the ≥ 50 years old age group, colorectal, lung, nasopharynx, prostate and liver cancers were predominant among men, while breast, colorectal, cervix, lung and ovarian cancers were common in women.

Although the common treatment modalities such as surgery and/or chemo and radiotherapies have played major roles in reducing the mortality and morbidity burden to a significant extent, complete cure is still uncertain. The prognosis varies depending upon the stage and the type of the disease, as well as the genetic makeup of the individual and environmental influences. Even when patients experience tumour regression immediately after therapy, recurrence or metastasis (spreading to other parts of the body) may occur later.

Immune system and cancer

Almost every day, several cancer cells are formed in our body. This is because thousands of cell divisions take place in the body daily and a few of such divisions result in mutated cells, leading to the birth of cancer cells.

However this problem is immediately tackled by the body’s immune system. The immune system is a complex network of cells and organs comprising of lymphocytes, macrophages, Dendritic cells, Natural Killer cells (NK Cell), Cytotoxic T Lymphocytes (CTL), and lymph nodes that work together to defend the body against attacks by “foreign” or “non-self” invaders including cancer cells.

Immediately upon recognition of a cancer cell, the lymphocytes are activated and engulf the cell. The NK cells will also attack the cancer cell to kill it. However when the immune system’s efficacy is overwhelmed by the abundance of cancer cell formation, or when the immune system becomes weak, cancer could then evolve as a disease and start growing.

Given the variable nature of cancerous cells, each cancer behaves somewhat uniquely.

In general, a multi-pronged approach to cancer is vital as each type of cancer grows at different rates and responds to different treatments and people with each specific cancer need specific combinations of treatment aimed at their particular kind of cancer. When the spread of cancer is widespread, total removal of the cancer growth by surgery may not be possible. At times, after removing a portion of the cancer growth, radiotherapy and/or chemotherapy may be necessary to treat the remnant portions of the cancer.

It has been widely recognised that chemotherapy of cancer has toxic side effects and has limitations in efficacy. Radiotherapy, although a very effective mode of treatment in certain types of cancer, also possess its own adverse effects. In general, the main disadvantage that these two modalities impose is that they affect not only the cancer cells, but also the normal cells in the body.

Multi-pronged approach

As there is no single fool-proof methodology of treatment for cancer, a multi-pronged approach is essential. In developing this approach, the latest scientific advancements have produced Immuno Cell therapy. Known as biological therapy, such therapies present less toxic side effects as compared to conventional cancer therapies.

Immuno Cell therapy is a promising new addition to the family of cancer treatments that includes surgery, chemotherapy, radiotherapy, and cancer vaccines. This mode of treatment uses the body’s immune system, either directly or indirectly, to fight cancer by enhancing the immune mechanisms of the body.

As this therapy uses only the patient’s own cells for treatment, it is safe and does not result in any allergy. Combining this with conventional therapy (ies) appropriately as per the patient’s condition, type of cancer, and regimen of chemo/radio therapies, improves outcome, as it has the advantage of the immune cells of the patient not affecting the normal functioning cells of the body upon transfusion.

Origin of immunotherapy

For most of the 20th century, there was no concrete evidence that human cancer antigens existed or that there were any measurable immune responses against growing cancers in patients. A major development in this field was the identification of the antitumour properties of interleukin-2 (IL-2), a secreted cytokine produced by helper T lymphocytes, which is a major regulator of immune reactions.

The interaction of antigens with T lymphocytes activates lymphoid cells to express receptors for IL-2, and the simultaneous stimulation of IL-2 secretion leads to the expansion of immune cells and effective immunity. Animal studies done by Dudley and colleagues from the US National Institute of Health demonstrated that the antitumour impact of IL-2 administration is a result of stimulating immune reactions in vivo. These and other studies have led to the development of immunotherapy to treat cancer.

Autologous immune enhancement therapy (AIET)

Autologous Immune Enhancement Therapy (AIET) has a successful clinical history in Japan and the US for the past two decades. Immuno cell therapy of cancer using autologous lymphocytes activated in the laboratory was first introduced by Rosenberg et al., of the US National Institute of Health.

In the late 80s, they published a hallmark article in which they reported a low tumour regression rate (2.6 to 3.3 %) in 1,205 patients with metastatic cancer who had undergone different types of active specific immunotherapy (ASI).

This led to suggestions that AIET combined with specific chemotherapy have synergistic potential.

AIET has an added advantage since patient’s own cells (autologous) have less chance of rejection and safer as compared to donor cells.

The name AIET was coined for the following reasons:

1. The term “AUTOLOGOUS” signifies that the patient’s own immune cells are used.

2. Serum from the patient’s own blood is also used to culture cells obtained from the same source.

3. In this approach, there are no foreign components. Therefore it is a safe mode of treatment without adverse reactions (eg rejection or allergy) and do not require the use of immune suppressors.

The term “immune enhancement” signifies the direct boosting of the immune system by cultivating the isolated immune cells of the patient in the lab and expanding the numbers by multifold before transfusing it back into the patient to yield maximum results.

The cell-based immunotherapy expansion approach in the lab using Natural Killer Cells (NK) and Cytotoxic T Lymphocytes (CTL’s) has been mastered by Dr Hiroshi Terunuma and his team starting from early 90’s. The Biotherapy Institute of Japan started the therapy in 2000 and has treated more than 10,000 patients to date with no adverse reactions reported.

There are three requirements for an effective immunotherapy for cancer: (i) A sufficient number of the appropriate tumour reactive lymphocytes (cancer fighting cells) must be present in the peripheral blood of the patients, (ii) Lymphocytes must be capable of reaching the site of the cancer, and (iii) Lymphocytes at the tumour site must have appropriate effector mechanism (eg production of cytotoxic granules) to destroy cancer cells.

Research, clinical trials and established clinical treatment methodologies for cancer using immunotherapy have also been reported from institutions in other parts of the world. Nichi-Asia Life Science Sdn Bhd (NiSCELL) has taken the initiative to introduce AIET to Malaysia for the first time. This is done with technical collaboration with GN Corporation Japan, Biotherapy institute Japan, and Nichi In Center for Regenerative Medicine India.

According to CEO of NiSCELL, Vincent Chang, “This is the first and only such facility in Malaysia for AIET.

“We will be officially launched tomorrow and we hope to provide a vital service to oncologists and doctors practising in this country.

“We believe that AIET will offer patients and doctors another effective modality in the ongoing fight against cancer.”

In 1999, the first private clinic in Japan with a cell processing facility and specialising in immune-cell therapy was established. Dr Terunuma headed the Biotherapy Institute of Japan, who, apart from offering AIET, has been exploring in depth the finer components of innate immunity against cancer in the form of Cytotoxic T Lymphocytes.

Since then, the number of such institutes has increased several fold as many cancer patients are opting for this kind of less toxic treatment.

Development of this new line of therapy in Malaysia would be a boost in combating cancer. A currently practised treatment method in cancer-specific immuno-cell therapy uses Activated Lymphocytes (AL), Natural Killer cells (NK), and Dendritic Cells (DC), which are the major immune cells that play key roles in destroying cancer cells.

Natural Killer cell is an important component of the innate immune system and plays a central role in host defence against tumour and virus infected cells. NK cells release perforin, which punches large holes through the cancer cell membrane and then injects large quantities of granzymes, which degrade the DNA and other cellular components through these holes, leading to death of the cancer cell.

One of the largest studies in Japan involving 1,400 patients has shown that when combined with conventional treatment, the efficacy of AIET improves by approximately 20 to 30%.

According to a consultant oncologist, the therapy is very new in Malaysia. “It hasn’t been widely used here. It’s something very new.”

Limitation of AIET

A major limitation to the development of effective lymphocyte transfer therapies for patients with cancer has been the inability to mediate the prolonged persistence of the transferred cells. A pilot clinical trial in 13 patients with metastatic melanoma studied by Dudley and colleagues suggested that conditioning with non-myeloablative chemotherapy before adoptive transfer of activated tumour-reactive T cells enhances tumour regression and increases the overall rates of objective clinical responses.

The study demonstrated that there was a significant correlation between tumour regression and the degree of persistence in peripheral blood of adoptively transferred T cell clones, suggesting that inadequate T cell persistence may represent a major factor limiting responses to AIET.


1. Dewan MZ, Terunuma H et al. Potential role of NK cells in growth and infiltration of AIDS – associated primary effusion lymphoma cells: Implication of Immune therapy. Cancer Sci. 2006; 97(12):1381-7.

2. Dewan MZ, Terunuma H et al. Natural killer cells in breast cancer cell growth and metastasis in SCID mice. Biomedicine and Pharmacotherapy. 2005; 59: S373-S377.

3. Hiroshi Terunuma, Xuewen Deng et al. Adoptive immunotherapy of cancer with ex vivo expanded, Autologous NK cells. The Society for Natural Immunity 2005; 9th Meeting, NK Hawaii B070.

4. Shigenori Goto, Toru Kaneko et al. Combined Immunocell therapy using Acitvated Lymphocytes and Monocyte-derived Dendritic cells for Malignant Melanoma. Anticancer Res 2005; 25: 3741-3746.

5. Steven A. Rosenberg. Shedding light on Cancer. N engl j med 2004; 14: 1461-1463.

6. Rosenberg, S.A., Yang, J.C. & Restifo. Cancer Immuno therapy: moving beyond current vaccines. N.P. Nat. Med. 2004; 10, 909–915.

7. Steven A Rosenberg. Development of Effective Immunotherapy for the Treatment of Patients with Cancer. J Am Coll Surg. 2004; 198:685-696

8. Mark E.Dudley and Steven A. Rosenberg. Adoptive cell transfer therapy for the treatment of patients with cancer. Nature 2003; 3: 666-675.

9. Kohji Egawa. Immuno-cell therapy of Cancer in Japan. Anti Cancer Res 24:3321-3326

10. Shigenori Goto, Noriko Shirotani et al. Clinical Benefit of Nontoxic Therapy in patients with advanced cancer. Anti cancer Res 2002; 22: 2461-2464.

11. Steven A. Rosenberg. Progress in human tumor immunology and immunotherapy. Nature 2001; 411(6835): 380-384.

12. Michael Schleuning. Adoptive allogeneic immunotherapy – history and future perspectives. Transfusion science 2000; 23: 135-150.

13. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000 25; 356(9244):1795-9.

14. Montelli TC, Peracoli MT, Gabarra RC, Soares AM, Kurokawa CS, “Familial Cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members”, Arq Neurosiquiatr2001 59(1).

15. Malaysian Cancer Statistics - Data and Figure Peninsular Malaysia 2006. Published by: National Cancer Registry, Ministry of Health Malaysia.

- Courtesy staronline, 28 Feb 2011 issue.
*"Nichi" stands for Japan and "In" stands for India. This institute started on an Indo-Japan collaboration now has spreaded further with global alliances
    © NCRM. All right reserved.                                                                                                                                                                                          Disclaimer