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Treatment of neoplasms with viruses

a virus and neoplasm technology, applied in the field of virus treatment of neoplasms, can solve the problems of unsatisfactory treatment, unfavorable early detection of cancer, and much less effective cancer treatment, including chemotherapy and radiation

Inactive Publication Date: 2003-03-06
PRO VIRUS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0028] It is a further object of the invention to provide guidance in the genetic engineering of viruses in order to enhance their therapeutic utility in the treatment of neoplastic diseases.
[0192] Certain purine nucleoside analogs, e.g., 2-chlorodeoxyadenosine and 2'-deoxycoformycin, reduce interferon production in vivo. Such compounds are used to further effect differences in interferon sensitivities of tumor cells versus normal cells and are optionally used as an adjunct to viral therapy.

Problems solved by technology

However, early detection of cancer is not always possible, and even when it is, treatments are unsatisfactory, especially in cases of highly malignant cancers.
Cancer treatments, including chemotherapy and radiation, are much less effective in latter stages, especially when neoplastic growths are large and / or constitute a high tumor burden.
Since the mechanism of tumoricidal activity was thought to be immunologic, no work was carried out to address direct tumor cytotoxicity of the virus.
Also, injection of one transduced human tumor cell into the tumor mass of another, non-transduced tumor resulted in a small decrease in size.

Method used

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  • Treatment of neoplasms with viruses
  • Treatment of neoplasms with viruses
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Examples

Experimental program
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Effect test

example 2

[0203] Use of PPMK107 for the Intratumoral Treatment of Human Tumor Xenografts (5 mm) in Athymic Mice

[0204] Athymic mice were injected intradermally with 10 million human tumor cells. After tumors reached a size range from between 5 and 10 mm, a single injection of PPMK107 (at a dose of 3.times.10.sup.8 PFU) or saline was given. Almost all tumor types exhibited a rate of complete or partial regression of 50% to 100% (see Table 7) in mice treated with PPMK107. The one exception is the case of the U87MG experiment (experiment I): Although only one of 9 tumors treated with PPMK107 completely regressed, two more virus-treated tumors showed regression of 32% and 20% and two more virus-treated tumors had slower growth than all 8 tumors treated with saline control. Tumor regression was virtually absent in the saline control treated tumors: In all of these experiments (A through I listed in Table 7) only one of 73 control tumors showed regression. These results indicate that diverse tumor t...

example 3

[0206] Use of PPMK107 for the Intravenous Treatment of Human Tumor Xenografts (5.5 mm) in Athymic Mice

[0207] Athymic mice were injected intradermally with 10 million human HT1080 fibrosarcoma cells. After tumors reached a size range from between 5 and 8 mm, a intravenous injection(s) of PPMK107 or saline were made. As shown in Table 8, at the highest virus dose level (1.times.10.sup.9 PFU) complete tumor regression was seen in all seven mice. Single injections of 3.times.10.sup.8 and 6.times.10.sup.7 resulted in regression rates of over 90%. While a single IV injection of 3.times.10.sup.8 only a 55% rate of tumor regression, three IV injections at this dose level yielded a 100% rate of response. Mice treated with IV saline exhibited no evidence of tumor regression. These results indicate that subcutaneous HT1080 tumors are very responsive to IV treatment with PPMK107.

8TABLE 7 PPMK107 intratumoral treatment of subcutaneous human tumor xenografts (<10 mm and <5 mm) in athymic mice Com...

example 4

[0209] First Experiment Using PPMK107 for Intratumoral Treatment of Large A375 Melanoma Xenografts in Athymic Mice

[0210] Athymic mice were injected intradermally with 10 million A375 human melanoma cells. Ten days later, tumors of various sizes were treated with a single injection PPMK107 (doses of 3.times.10.sup.8, 9.times.10.sup.8, and 1.5.times.10.sup.9 PFU) or saline. For those tumor with a single largest dimension of 10 to 11 mm, all nine completely regressed in response to intratumoral treatment with these doses of PPMK107, while of those tumors with a single largest dimension of 8 to 9.5 mm, twelve out of 24 completely regressed in response to virus therapy (P<0.008; Table 9, section A). No tumor regression was seen in any mouse treated with saline.

[0211] These same tumors when sorted by tumor volume also indicated a high percentage of complete regression in those of larger tumor volume. In response to these doses PPMK107, complete regression occurred in 14 out of 17 tumors w...

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Abstract

The subject invention relates to viruses that are able to replicate and thereby kill neoplastic cells with a deficiency in the IFN-mediated antiviral response, and their use in treating neoplastic disease including cancer and large tumors. RNA and DNA viruses are useful in this regard. The invention also relates to methods for the selection, design, purification and use of such viruses for cancer therapy.

Description

[0001] The subject invention relates to viruses that are able to replicate in and cause the death of neoplastic cells with a deficiency in the interferon (IFN)-mediated antiviral response. RNA and DNA viruses are useful in this regard. The invention also relates to the use of these viruses for the treatment of neoplastic diseases including cancer and large tumors.[0002] Neoplastic disease which includes cancer is one of the leading causes of death among human beings. There are over 1.3 million new cases of cancer diagnosed in the United States each year and 550,000 deaths. Detecting cancer early, before it has spread to secondary sites in the body, greatly increases a host's chances of survival. However, early detection of cancer is not always possible, and even when it is, treatments are unsatisfactory, especially in cases of highly malignant cancers. Cancer treatments, including chemotherapy and radiation, are much less effective in latter stages, especially when neoplastic growth...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/76A61K35/768A61K38/21A61K39/42C12N7/00
CPCA61K38/21A61K39/42C12N7/00C12N2760/18132C12N2770/36132A61K2300/00A61K35/768A61P43/00
Inventor ROBERTS, MICHAEL S.LORENCE, ROBERT M.GROENE, WILLIAM S.RABIN, HARVEYVON BORSTEL, REID W.
Owner PRO VIRUS
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