Drug – bio-affecting and body treating compositions – Nonspecific immunoeffector – per se ; or nonspecific...
Reexamination Certificate
2001-01-17
2004-11-02
Canella, Karen A. (Department: 1642)
Drug, bio-affecting and body treating compositions
Nonspecific immunoeffector, per se ; or nonspecific...
C424S094100, C424S282100
Reexamination Certificate
active
06811788
ABSTRACT:
TECHNICAL FIELD
The present invention relates to compositions and methods for treating neoplasms in mammals, particularly humans. More particularly, combinations for intratumoral administrations of agents that coagulate tumors and agents that enhance the inflammatory response are provided. Also provided are methods for treating neoplasms by administration of the combinations.
BACKGROUND ART
A number of approaches, including surgery, chemotherapy and radiation, to cancer therapy have been used. Surgery is a traditional approach in which all or part of a tumor is removed from the body. Surgery generally is only effective for treating the earlier stages of cancer. For more than 50% of cancer patients by the time they are diagnosed, they are no longer candidates for effective surgical treatment. Surgical procedures may increase tumor metastases through blood circulation during surgery. Most of cancer patients do not die from the cancer at the time of diagnosis or surgery, but rather die from the metastasis and the recurrence of the cancer.
Other therapies are also often ineffective. Radiation therapy is only effective for local cancer therapy at early and middle stages of cancer, and is not effective for the late stages of cancer with metastasis. Chemotherapy can be effective, but there are severe side effects, e.g., vomiting, low white blood cells (WBC), loss of hair, loss of weight and other toxic effects. Because of the extremely toxic side effects, many cancer patients cannot successfully finish a complete chemotherapy regimen. Some cancer patients die from the chemotherapy due to poor tolerance to the chemotherapy. The extreme side effects of anticancer drugs are caused by the poor target specificity of such drugs. The drugs circulate through most normal organs of patients as well as intended target tumors. The poor target specificity that causes side effects also decreases the efficacy of chemotherapy because only a fraction of the drugs is correctly targeted. The efficacy of chemotherapy is further decreased by poor retention of the anti-cancer drugs within the target tumors.
Immunotherapy, including the use of cancer vaccines, such as autologous vaccines, is effective for cancer patients with tumor burdens of less than 10
8
tumor cells. Immunotherapy is often used as an adjunctive therapy in combination with other therapies such as surgery, radiation therapy and chemotherapy to clear out the remaining tumor cells. Immunotherapy and the use of tumor vaccines have not proven effective against a tumor burden greater than 5×10
9
to 10
11
tumor cells, which is typical in a patient with small, symptomatic metastases. In addition, autologous tumor vaccination involves complicated procedures and requires a tumor specimen be processed for each patient to be treated.
Alcohol intratumoral injection therapy has been applied in clinical practices in the treatment of liver neoplasms and others cancers. Alcohol injection therapy alone does not kill all tumor cells because of the limiting volume of alcohol that can be injected, coagulating necrosis of normal living tissues caused by alcohol, alcohol dilution by the blood in the tumor to non-effective concentrations, especially when treating the large tumors and other factors. Alcohol cannot be injected close to critical structures, such as the central nervous system. Alcohol intratumoral injection therapy also has been administered with certain anti-tumor agents that are co-injected (Yu et al. (1994)
J. Current Oncology,
1:97-100). In these protocols, the coagulated mass of tissue resulting from the alcohol injection serves as a slow release depot for the anti-tumor agent.
At present, there is no effective treatment for patients with high tumor burdens. Since early stage tumors are not easily detectable, many patients who are diagnosed with cancer are at the later stages of cancer with the tumor burden greater than 5×10
9
to 10
11
tumor cells, or the tumor has already metastasized into other tissues. For these patients, traditional cancer therapies such as surgery, radiation therapy and chemotherapy may no longer be effective and/or suitable.
Despite some progress of cancer therapy, there are few, if any, effective treatments. Due to the severity and breadth of neoplasm, tumor and cancer, there is a great need for effective treatments of such diseases or disorders. An ideal cancer therapy should have the potency to eradicate systemic tumor at multiple sites in the body and the specificity to discriminate between neoplastic and non-neoplastic cells. Therefore, it is an object herein to provide treatments for such diseases and disorders. In particular, it is an object herein to provide a cancer therapy that has the potency to eradicate systemic tumor at multiple sites in the body and the specificity to discriminate between neoplastic and non-neoplastic cells.
DISCLOSURE OF THE INVENTION
Provided herein are combinations for intratumoral therapy that include agents that cause coagulation of tumor tissue and agents that enhance the inflammatory response to the resulting coagulated tissue mass. Preferred among the combinations are those that include three components (designated three in one or TIO) for intratumoral injection therapy and methods of treatment using the compositions. The combinations include an oxidizing agent or a reducing agent, a protein denaturing agent or other coagulating means or treatment, and a hapten. The combinations are used to treat tumors, e.g., solid tumors.
It is shown herein that these combinations, such as those that include one or more oxidizing agents and/or reducing agents, protein denaturing agents and haptens have broad applicability in the treatment of various types of neoplasms, tumors and cancers, particularly solid tumors that are not effectively treatable with traditional cancer therapy such as surgery, radiation therapy, chemotherapy and immunotherapy.
Provided herein are methods and compositions for treating neoplasms, tumors and cancers. Encompassed within the methods are the uses of any combinations of one or more oxidizing agents or reducing agents, protein denaturing agents and haptens that can alleviate, reduce, ameliorate, or prevent neoplasms, tumors and cancers; or place or maintain in a state of remission of clinical symptoms or diagnostic markers associated with such neoplasms, tumors and cancers, particularly solid tumors that are not effectively treatable with traditional cancer therapy such as surgery, radiation therapy, chemotherapy and immunotherapy. The combinations can be used alone or in conjunction with other treatments for neoplasms, tumors and cancers.
The neoplasms, tumors and cancers that can be treated include, but are not limited to, the neoplasm of adrenal gland, anus, auditory nerve, bile ducts, bladder, bone, brain, breast, bruccal, central nervous system, cervix, colon, ear, endometrium, esophagus, eye, eyelids, fallopian tube, gastrointestinal tract, head and neck, heart, kidney, larynx, liver, lung, mandible, mandibular condyle, maxilla, mouth, nasopharynx, nose, oral cavity, ovary, pancreas, parotid gland, penis, pinna, pituitary, prostate gland, rectum, retina, salivary glands, skin, small intestine, spinal cord, stomach, testes, thyroid, tonsil, urethra, uterus, vagina, vestibulocochlear nerve and vulva neoplasm. Preferably, the neoplasms, tumors and cancers to be treated is a solid tumor. The combinations are particularly effective for solid tumors, including solid tumor larger than 10
8
cells, e.g., from about 5×10
9
to about 10
11
cells.
The combinations are provided to improve the therapeutic efficiencies of cancer therapy for most cancer patients, including very earlier stage cancer patients with visible tumor mass who may not be candidates for surgery and late stage cancer patients with larger tumors or metastases for whom the opportunity for surgery may have passed.
Each component may be a separate composition or agent or may be combined. The combination is intended to induce coagulation of the tumor and to enhance the inflammatory
Canella Karen A.
Morrison & Foerster / LLP
Yu Baofa
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