Composition comprising tumor cells and extracts and method for using thereof

A technology of tumor cells and compositions, applied in the field of compositions containing tumor cells and extracts and its use, can solve the problems of reduced surface expression, inability to induce T helper cells, and restriction of T cell recognition

Inactive Publication Date: 2001-08-22
THOMAS JEFFERSON UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0013] 2) Human tumor cells are unable to prime T helper cells or provide co-stimulatory signals to said T cells, Fearon, E.R et al., Cell, 1990, 60, 397; Townsend, S.E and J.P. Allison, Science, 1993, 259, 368; and
[0014] 3) Decreased surface expression of major histocompatibility products on tumor cells, thereby limiting their recognition by T cells, Ruiter, D.J., Symposium on Cancer Biology, 1991, 2, 35, none of the above hypotheses have been validated in clinical systems confirmed
Although applicants have successfully treated certain melanoma patients using hapten-conjugated melanoma cells, there remains a need in the field of cancer therapy for additional and improved methods of inducing anti-tumor responses

Method used

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  • Composition comprising tumor cells and extracts and method for using thereof
  • Composition comprising tumor cells and extracts and method for using thereof
  • Composition comprising tumor cells and extracts and method for using thereof

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Embodiment 1

[0108]Low-dose cyclophosphamide (CY) was administered to 64 patients with metastatic melanoma, and then these patients were treated with the melanoma vaccine prepared according to the above method, and the immunotherapy efficacy and antitumor activity were monitored. On day 0, the patient was administered intravenous cyclophosphamide 300Mg / M 2 . Three days later, they were given an intradermal injection of a vaccine consisting of 10 x 10 6 to 25×10 6 Consisting of autologous, cryopreserved, irradiated (2500R) tumor cells; obtained by enzymatic (collagenase and DNase) dissociation of metastatic tumor masses. The sequence of treatments was repeated every 28 days for a total of eight treatments.

[0109] Following administration of cyclophosphamide, the toxicity of the treatment was limited to a local inflammatory response at the injection site and mild nausea and vomiting. There were 40 evaluable patients with measurable metastases; 5 of them responded, 4 of which were compl...

Embodiment 2

[0114] Metastatic melanoma patients were sensitized to DNP by topical application of 1% dinitrochlorobenzene (DNCB) or dinitrofluorobenzene (DNFB) to the upper arm. After 2 weeks, they were given a vaccine consisting of 10 x 10 mixed with BCG 6 to 25×10 6 Consisting of autologous, irradiated melanoma cells conjugated to DNP; 3 days prior to administration of DNCB (or DNFB) or vaccine, the patient was given intravenous cyclophosphamide 300Mg / M 2 . After 2 vaccine treatments (8 weeks), a strong inflammatory response developed in the tumor mass of 3 out of 4 evaluable patients. Patient #1 developed erythema and swelling in >50 large (1-3 cm) skin metastases on her legs and lower abdomen, followed by ulceration and drainage of necrotic material, some of which began to resolve. Biopsy showed that CD4+CD8+ T lymphocytes had infiltrated the tumor. Patient 2# developed erythema and swelling in the skin covering a large (8 cm) nodular mass in her lower abdomen and groin. These tum...

Embodiment 3

[0115] Fifteen patients (including 3 patients in Example 2) were treated with metastatic melanoma using a new form of immunotherapy, a tumor cell vaccine conjugated to DNP. Sensitization of metastatic melanoma patients to DNP by topical application of 5-dinitrochlorobenzene in the upper arm. Then give the patient cyclophosphamide 300Mg / M every 4 weeks 2 , 3 days later, the patient was injected with DNP-conjugated 10 × 10 6 to 25×10 6 Autologous, irradiated melanoma cells. Patients received 6-8 treatments. Most patients (92%) developed delayed-type hypersensitivity reactions (mean DTH = 17 mm) to autologous lymphocytes or tumor cells conjugated to DNP. In 11 / 15 patients, the vaccine induced a surprising inflammatory response in subcutaneous and nodal metastases consisting of erythema, swelling, warming and softening around the tumor mass and in one case pus Sexual drainage. Biopsy showed lymphocytic infiltration, which was mainly CD3+, CD4-, CD8+, HLA-DR+ T cells by immun...

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Abstract

The present invention is directed to compositions containing hapten-modified tumor cells and extracts and method of treating cancer by administering a therapeutically effective amount of a composition containing a tumor cell or tumor cell extract to a subject in need of such treatment. The tumor cells and extracts of the invention and compositions thereof are capable of eliciting T lymphocytes that have a property of infiltrating a mammalian tumor, eliciting an inflammatory immune response to a mammalian tumor, eliciting a delayed-type hypersensitivity response to a mammalian tumor and / or stimulating T lymphocytes in vitro. The invention also relates to an effective vaccination schedule useful for inducing an antitumor response in a mammalian patient suffering from cancer by inducing at least one of the following: tumor necrosis, tumor regression, tumor inflammation, tumor infiltration by activated T lymphocytes, delayed-type hypersensitivity response, and prolongation of patient survival.

Description

field of invention [0001] The present invention relates to compositions comprising hapten-modified tumor cells and extracts thereof, and methods of treating cancer by administering to a subject in need thereof a therapeutically effective amount of the composition comprising tumor cells or tumors cell extract. The present invention also relates to effective immunization regimens useful for inducing anti-tumor responses in cancer patients. Background of the invention [0002] Since the 1960's, the theory has evolved that tumor cells carry specific antigens (TSAs) that are not present on normal cells, and that an immune response against these antigens enables the individual to reject the tumor. Later, it was discovered that the anti-TSA immune response could be enhanced by introducing new immune determinants into the cells, Mitchison, Transplant, Proc., 1970, 2, 92. Such "helper determinants" can be haptens, proteins, viral coat antigens, graft antigens or xenogeneic cell ant...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/07A61K31/675A61K35/12A61K39/00A61K39/385A61P35/00C12N5/09
CPCA61K39/0011A61K2039/6012A61P35/00A61K39/00
Inventor D·伯德
Owner THOMAS JEFFERSON UNIV
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