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Method of inducing an anti-tumor response against a lung metastasis in a melanoma patient

A melanoma and anti-tumor technology, applied in anti-tumor drugs, pharmaceutical formulations, cancer antigen components, etc., can solve problems such as high dose of BCG, excessive dose of leukemia cells, and unsuccessful conventional treatment

Inactive Publication Date: 2001-06-27
THOMAS JEFFERSON UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In retrospect there were some technical issues with these trials: 1) allogeneic leukemic cells were used instead of autologous leukemic cells; 2) the dose of leukemic cells in the vaccine was excessive (up to 10 9 cells / dose); 3) BCG dose was very high and the time and site of BCG administration were separate from leukemic cell vaccine; and 4) the vaccine was administered while the patient was receiving cytotoxic drugs (maintenance or consolidation chemotherapy)
[0012] Conventional treatments used to treat human cancers are generally unsuccessful

Method used

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  • Method of inducing an anti-tumor response against a lung metastasis in a melanoma patient
  • Method of inducing an anti-tumor response against a lung metastasis in a melanoma patient
  • Method of inducing an anti-tumor response against a lung metastasis in a melanoma patient

Examples

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Embodiment 1

[0072] Sixteen patients with melanoma with lung metastases were treated according to the present invention. Lung metastases were detectable in all treated patients. For the purposes of the present invention, the term "detectable" pulmonary metastases refers to x-ray visible metastases. Melanoma cells were isolated from lymph nodes and lung metastases and prepared as described above. Cells were obtained by enzymatic dissociation of metastatic diseased masses (with collagenase and DNase). Cells were bound to DNP as described herein. Some patients were sensitized to DNP by topical application of 5% dinitrochlorobenzene to the upper arm. Low-dose cyclophosphamide (CY) preceded the first vaccine. On day 0, the patient was given an intravenous injection of 300Mg / M 2 of cyclophosphamide. Three days later, an intradermal injection containing 2.5 x 10 6 to 25×10 6 Vaccine of autologous cryopreserved irradiated (2500R) tumor cells. Most patients were treated weekly for a total ...

Embodiment 2

[0075] Tumor masses used to prepare vaccine compositions of the invention can be obtained from lymph node, lung or subcutaneous metastatic masses and prepared as described above. Briefly, cells can be extracted by enzymatic dissociation with collagenase and DNase and by mechanical dissociation. Cell membranes can be isolated as described in this manual, frozen in a controlled rate freezer, and stored in liquid nitrogen for later use. On the day patients were treated, membranes were thawed, washed and resuspended in Hanks' balanced salt solution without phenol red. Modification with DNP can be performed by the method of Miller and Claman (1976). The method involves incubating melanoma cells with dinitrofluorobenzene (DNFB) for 30 minutes under sterile conditions followed by washing with sterile saline.

[0076] Patients with small and multiple lung metastases melanoma and patients with lung metastases can be treated as follows. The vaccine composition may contain a minimum o...

Embodiment 3

[0083] The four patients who responded to the vaccine of the invention according to Example 1 continued to be monitored to evaluate the potency of the vaccine. Three patients (patients 2, 3 and 4 in Example 1) received a total of 6 vaccinations, once a week, and a booster vaccine at 6 and 12 months from the initial vaccination. One patient (Patient 1) received weekly vaccines for twelve weeks without booster vaccines. Two patients had complete resolution and two patients had partial resolution. Patient 1 (in Example 1) had partial regression for 12 months. Patient 2 (in Example 1) had partial regression for 8 months. Patient 3 (of Example 1) had complete remission for 29 months and the fourth patient (of Example 1) had complete remission for more than 27 months. The term "complete regression" refers to complete disappearance of all detectable tumors. The term "partial regression" generally refers to at least a 50% reduction in tumor diameter. In any case, in the context o...

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Abstract

The present invention is directed to a method of inducing an anti-tumor response against a metastatic melanoma by administering an effective amount of a composition comprising at least one of the following: (i) a hapten-modified syngeneic mammalian melanoma cell substantially in a no growth phase, (ii) a hapten-modified melanoma cell membrane, (iii) a peptide isolated from said hapten-modified melanoma cell or membrane and (iv) a T cell capable of mediating an anti-tumor response such as for example regression of a melanoma. The metastatic melanoma treated according to the present invention includes metastatic melanoma which is limited to the lung and is preferably a small lung metastasis. The invention is further directed to a melanoma cell, an isolated melanoma cell membrane, a peptide isolated from such cell or membrane and a T cell having the property of inducing an anti-tumor response, a composition containing such cell, membrane, peptide, T cell or combination thereof, as well as the methods for theirisolation and preparation.

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35 U.S.C. §119 to Provisional Patent Application Serial No. 60 / 081,256, filed April 9, 1998, the entire disclosure of which is incorporated by reference. Government Funding Reference [0003] The invention described herein was made in the course of work funded or awarded under NIH grant number CA29348 by the American Institute of Public Health. The US Government has certain rights in this invention. Background of the invention [0004] In the 1960s, it was theorized that tumor cells bear specific antigens (TSAs) that are not present on normal cells and that an immune response to these antigens might help to reject the tumor. It was later suggested that the immune response to TSA might be enhanced by the introduction of new immunological determinants on the cells. Mitchison, Transplant. Proc., 1970, 2, 92. Such determinants, although still unknown, are called "auxiliary determina...

Claims

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Application Information

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IPC IPC(8): A61K31/675A61K35/24A61K35/28A61K39/00A61K39/39A61P35/00A61P35/04
CPCA61K39/0011A61K2039/6012A61K2039/5152A61P35/00A61P35/04A61K2039/876A61K39/00119
Inventor D·伯德
Owner THOMAS JEFFERSON UNIV