Cancer accounts for 1 of every 4 deaths in the United States. The National Institutes of Health estimate overall costs for cancer in 2006 at more than $206 billion: $78 billion for direct medical costs; $18 billion from lost productivity due to illness; and $110 billion for the cost of lost productivity due to premature death. About 1,445,000 new cancer cases are expected to be diagnosed in 2007. Approximately 560,000 Americans will die of cancer in 2007. Nearly half of patients who endure surgical tumor removal experience local tumor recurrence or metastasis.

Immune Therapy Products – Present Trend

One solution is embodied in anticancer immunotherapy, a very promising methodology for use in obtaining effective, highly specific treatments for malignant tumors, with negligible side effects. Recently developed pharmaceutical products are capable of (1) stimulating T cell and antibody production (e.g., dendritic cell vaccines, genetic vaccines, cytokines and biological response modifiers), or (2) employing artificially produced antibodies with a predetermined specificity (monoclonal antibodies), with minimal side effects. Both approaches offer potentially attractive therapeutic products. Further, these vaccines and monoclonal antibodies are essentially “natural” molecules that are not burdened with the non-specific drug/target interactions that have often complicated traditional anti-cancer drug development.

Nonetheless, the performance of these vaccines, cytokines and biological response modifiers falls short in most cases due to a fundamentally overlooked problem. A cancer patient's immune system is impaired in a way that it cannot on its own effectively reject the tumor. Further, there is a pernicious mechanism in a cancer patient's immune system response that actually promotes tumor recurrence, growth and metastasis.

BioCrystal's technology is based on experimental discovery showing that so-called B-lymphocytes, which produce antibodies against pathogens, develop an aggressive behavior in response to the presence of a tumor cell. In the course of adenocarcinoma (e.g., breast, colon, prostate, lung, stomach, reproductive tract) cancer development, B-lymphocytes become polarized into making antibodies against certain types of tumor-associated antigens in an absorbent feedback, in a kind of endless loop. These antibodies, however, do not effectively kill tumor cells. Instead, they sustain a chronic inflammatory process that facilitates both tumor invasion and metastasis. BioCrystal refers to this newly discovered process as a “pro-tumor immune response.” BioCrystal's discovery of this pro-tumor immune response was first published in Cancer Immunology and Immunotherapy, 2000, 48:541-549; and in Neoplasia, 1999,1:453-460.

Current anticancer therapies basically target the destruction of tumor cells and marginally address the tumor concomitant systemic pathology. BioCrystal has discovered the means for controlling tumor biology, including system pathology that can be applied in cancer therapy to avoid tumor recurrence and metastasis.

Immune Corrective Therapy - Advantages

In individuals with progressive cancers the immune response mechanism is flawed, and attempts to intervene often produce a pro-tumor immune response. Immune corrective therapy modulates this anticancer immune response, suppressing inflammatory pathways and activating the appropriate cell rejection mechanisms to attack the foundation of the cancer invasion process.

In the presence of a faulty immune response, malignant tumors can reappear after a period of time. Immune corrective therapy accomplishes two things:(1) it controls the inflammatory response that encourages this invasion, and (2) induces the proper immune response to detect and destroy anchored tumor cells. BioCrystal has proven experimentally that immune corrective therapy significantly reduces cancer recurrence.

A first class of proprietary anticancer treatments is designed for use as an adjuvant therapy in conjunction with commonly recommended anticancer treatments – surgery, chemotherapy, or a combination thereof. This class of anticancer treatments interferes with the B-lymphocytes that serve to fuel the pro-tumor immune response . After tumor resection, this adjuvant procedure is administered to control the pro-tumor immune response and prevent tumor recurrence. Within this class of anticancer therapies is a treatment that attacks tumor cells, B cells in and around the tumor, and other immune effector cells that may be involved in a pro-tumor immune response . This novel therapy has also been the subject of publication ( Cancer Immunology and Immunotherapy, 2000, 48:541-549). A related publication (Cancer Research, 2002, 62:7042-7049) discusses other factors contributing to tumor angiogenesis, tumor growth and metastasis.

The surgical removal of primary tumor is intended to substantially remove all of the tumor tissue, but residual tumor cells can remain hidden in contiguous tissues or distant organs. In the presence of a normal immune response these cells are rejected and the cancer is cured. Unfortunately, that does not always occur. Present in the vicinity of the tumor is lymphoid tissue (lymph nodes). These nodes can harbor immune cells (B-lymphocytes) that have the potential to trigger a pro-tumor immune response, resulting in cancer recurrence and metastasis. Removal of the tumor alone, then, may not be sufficient to prevent cancer.

When ICS is employed, an individual scheduled for surgery receives a tracer compound that specifically targets lymphoid tissues harboring immune cells with the potential to trigger a pro-tumor immune response. Following primary tumor resection the surgeon employs an ICS procedure, which detects any tracer compound-linked lymphoid tissue. These tissues are surgically removed, eliminating major deposits in the body capable of fostering cancer recurrence. Use of the coupled surgery/ICS treatment has resulted in a significant reduction in cancer recurrence, as shown in a limited clinical test involving colorectal cancer published in the American Journal of Surgery (1998).

The lymph nodes of cancer patients contain immune complexes made up of soluble tumor antigen (S-TAA) and antibody (Ab) that recognizes this antigen. These complexes can be used to detect lymphoid tissue harboring pro-tumor immune cells. Prior to surgery, a proprietary, radiolabeled tracer compound is injected into the patient (A). The tracer seeks out and binds to the pro-tumor lymph nodes (B). The surgeon uses a probe to detect the labeled tissue that will be surgically removed (C).

BioCrystal has pioneered a diagnostic test based on its discoveries involving the pro-tumor immune response. B cells are a population of specialized cells in the immune system that normally function to eliminate foreign disease-causing substances including microbes. The overall population of B-lymphocytes is comprised of various subpopulations, defined by their maturity or the foreign substance that activates them. Each subpopulation of B-lymphocytes can express a fingerprint or phenotype (e.g., a specific pattern of molecules at the cell surface) that can be used to differentiate it from other B-lymphocyte subpopulations. BioCrystal has learned that cancer patients experience several pro-tumor immune response-related changes in B-lymphocyte subpopulations, and has developed a proprietary diagnostic test for measuring this B-lymphocyte pathology. This test has three different uses:

Polynucleotides for Inhibition of Tumor Cell Growth and Metastasis

It has been demonstrated that Fas Ligand (FasL) expression causes a more aggressive phenotype in tumor cells. It has been proposed that the increase in malignancy is due to induction of T cell apoptosis by tumor cell-derived FasL. BioCrystal demonstrated experimentally that the administration of FasL antisense and FasL sense polynucleotides into and around a solid FasL negative tumor effectively produced a reduction in the tumor growth rate and suppression of invasion and metastasis compared with controls.

This procedure is proposed for use in the treatment of cancer patients with a primary tumor comprised of a solid, non-lymphoid tumor and/or its metastases, or to individuals who have been treated for a solid, nonlymphoid tumor and thereby inherently carry the risk of recurrence because of circulating tumor cells. In either case such individuals are at risk for developing, or have developed, a pro-tumor immune response. Such treatment has been shown experimentally to effect the Fas-mediated destruction of both the tumor and tumor-promoting B cells in the vicinity of the tumor. This treatment has been the subject of publication (Gene Therapy, 2001, 8:209-214). Sense and antisense therapies may be applied in a site-directed manner, rather than systemically.