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Home HITV Cancer Therapy How HITV Works

Tuesday22 August 2017

How HITV Works

Introduction

HITV (Hasumi™ Immuno-Therapeutic Vaccine) therapy was developed by Dr. Kenichiro Hasumi, ICVS Tokyo Clinic. The current highly effective protocol involves intratumoral injection of immature autologous dendritic cells in combination with Tomotherapy. Since 2008 over 500 late stage cancer patients have received this therapy in ICVS Tokyo Clinic and a remarkably high CR/PR rate has been noted.

Since the discovery of dendritic cells by Dr. R. 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 tumor cells by T cells gave rise to great hopes that it would be an ideal cancer treatment.

Hiccups in the Early Stages

Early dendritic cell based anti cancer therapy had not lived up to initial expectations. These early treatment protocols involved in vitro (in test tube) loading of the dendritic cells with whole cell tumour lysate and infusing the mature antigen presenting cells in blood stream of the patient.

Dendritic Cells That Attack Cancer
[ Image source from the National Cancer Institute, US ]

Various theories have been postulated as to why earlier dendritic cell treatment protocols have failed.

A. Dendritic cells may not perform well in the in-vitro or test tube environment and there may be antigenic differences between live in-vivo tumor cells and dead in-vitro tumor cells.

B. When dendritic cells are injected intravenously, many dendritic cells may be trapped in the pulmonary circulation and as a consequence not enough dendritic cells are able to reach the tumour site. The number of dendritic cells reaching the tumour is obviously a basic determining factor in effectiveness of this treatment.

Generation of dendritic cell
 

C. No expression of MHC Class I molecule on tumor stem cell. The immune system's dendritic cells and cytotoxic T cells (CTL) have one big blind spot when attacking tumour cells. In order to identify the enemy, CTL's check for protein combined with MHC class-I molecule expressed on the surface of target cells. The tumor stem cells do not express any MHC Class-I molecule and are able to escape detection by the immune system.

Activation of TCells Cytotoxic
[ Image source from the National Cancer Institute, US ]

D. Regulatory T-cells express CD4, CD25 and Fox3, and suppress the activation of other T-cells. This suppressor factor is important to prevent overreaction by immune system. Scientists have discovered that tumors contain large numbers of regulatory T-cells, which work negatively by suppressing the activation of pre-CTL's and helper T-cell.

Regulatory Tcells
[ Image source from the National Cancer Institute, US ]

E. In some patients, the tumor cells have already moved outside the treated sites and undergone further mutation enroute to new sites. The micro metastases will show up later as new tumor lesions.

Direct intratumoral injection of immature dendritic cells allows for adequate numbers of DC’s to reach the tumor 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.

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 tumors.

In the case of (e), a second round of HITV treatment can be considered to wipe out the newly mutated cancer cells.

HITV Lab

HITV Lab is involved in cell-based biotechnology medical applications with special focus on Dendritic Cell-Based Immunotherapy for cancer. HITV Lab is committed to support an international collaboration in the FDA clinical trial of HITV Therapy in late-stage cancer patients led by the University of Maryland, USA.

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