What is AFTV (Autologous Formalin-fixed Tumor Vaccine) ?
(1) A very unique cancer(tumor) vaccine
It is a new and innovative cancer vaccine consisting of formalin-fixed or paraffin-embedded tissue fragments derived from patient's own cancer (tumor) and immunoadjuvants. It is one of the self-vaccines (auto-vaccines) without any problematic adverse side effects.
(2) AFTV is ultimately "personalized" drug against cancer.
AFTV is injected to the patient from whom the cancerous tissue has been surgically resected.
AFTV contains all the unknown cancer-associated antigens restricted to that specific patient. The immune cells in that patient will discriminate the cancer cells from the normal cells after the AFTV injection (once every two weeks for a total of 3 injections in an out-patient basis).
The vaccine is promising to suppress the recurrence, to prevent the metastasis, and to treat the residual cancer cells of many types of human cancers after surgical resection.
<Background of Research and Development>
Tumor vaccines aiming to enhance cellular immune responses reported so far consist of either irradiated tumor cells [1-5], tumor cell lysates [1] co-injected with adjuvant [6, 7], genetically modified tumor cells [8, 9], tumor-associated antigenic peptides [10], peptide-loaded dendritic cells [11], or dendritic cells fused with tumor cells [12, 13]. Among these tumor vaccines, tumor-associated antigenic peptides are, unfortunately, only effective for patients carrying matched major histocompatibility complex (MHC) alleles [10], and peptides and tumor cell lysates are rather weak immunogens.
In contrast, antigen pre-loaded dendritic cells may be theoretically promising vaccines [11] although the formulation of this vaccine requires complex bench procedures including live cell handling. If one concerns on usage and acceptability as a treatment in clinical practice, simplicity in administration technique as well as in preparation such as bed-side handling of the vaccine should be key factors. In this respect, DNA vaccines are simple but, to our regret, occasionally fail to provide sufficient amounts of antigens [14].
After administering the tumor vaccine, scientists expect in vivo induction of cytotoxic T lymphocytes (CTL) which recognize and kill the targeted tumor cells in a very specific manner. It has been confirmed and accepted that CTL are far more cytotoxic than lymphokine-activated killer (LAK) cells against cancers [15-24].
In animal models, many laboratories have shown that CTL are the major effector cells to suppress cancerous tissue formation challenged with transplantable tumor cell lines and their metastasis and to cure the established tumors.
We, as well as others, have confirmed the effectiveness of in vitro induced autologous CTL in patients harboring recurrent malignant gliomas [25]. Also, we found that freshly extirpated and minced brain tumor tissues could be useful targets for induction of autologous CTL from the peripheral blood mononuclear cells (PBMC) [26].
Furthermore, it was indicated that formalin-fixed paraffin-embedded tumor sections were applicable as the source of tumor antigens [27, 28], and fixed cultured cancer cells could stimulate the expansion of autologous CTL [29]. It also has been reported that human CTL can be generated on the fixed adherent blood cells previously loaded with a tumor antigen [30, 31].
Concerning the impact in clinical practice, simplicity in preparation and bedside handling of the cancer vaccine is an important factor. In this respect, vaccines including live cells in the formulation are disadvantageous because of the complicated preparation techniques.
AFTV has been invented as a novel, simple, stable, and clinically effective autologous tumor vaccine based on these scientific knowledge.
