Increased Incidence of Pathological and Clinical Prostate Cancer With Age: Age Related Alterations of Local Immune Surveillance

Leibovitz, Arthur; Baumoehl, Yehuda; Segal, Refael

doi:10.1097/01.ju.0000131908.19114.d3

Cited by 20 publications

(20 citation statements)

References 33 publications

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“…Furthermore, the observed diVerence in survival between the subcutaneous and the intraprostatic challenge could also be an eVect of a blood-prostate-barrier, which is assumed to restrict the passage of leukocytes for immune surveillance of the prostate [9,12,23]. By using an immunological attractant like GM-CSF this barrier might be broken, making the prostate better accessible.…”

Section: Discussionmentioning

confidence: 99%

A prostate cancer vaccine comprising whole cells secreting IL-7, effective against subcutaneous challenge, requires local GM-CSF for intra-prostatic efficacy

Schroten-Loef

Ridder

Reneman

et al. 2008

Cancer Immunol Immunother

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A panel of cytokine-secreting RM-9 prostate cancer cells were tested as whole cell vaccines to determine their capacity to evoke an anti-prostate cancer immune response. In our model, vaccines secreting mGM-CSF or mIL-7 resulted in the highest increase in circulating T lymphocytes after vaccination, prolonged survival and, in a proportion of animals, tumor-free survival. Anti-tumor eVects were more evident after a subcutaneous RM-9 challenge than after an intraprostatic challenge. However, when the RM-9/mGM-CSF cell line was used as intraprostatic tumor challenge, protection after RM-9/mIL-7 vaccination was restored.

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Section: Discussionmentioning

confidence: 99%

A prostate cancer vaccine comprising whole cells secreting IL-7, effective against subcutaneous challenge, requires local GM-CSF for intra-prostatic efficacy

Schroten-Loef

Ridder

Reneman

et al. 2008

Cancer Immunol Immunother

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“…3,4 The incidence of prostate cancer is rare until age 40, but increases to 30% of all males by age 50 and to 75% by age 80. 5 With extension of the average life span, it has become the most common cancer among males of the Western world accounting for 35% of all cancers. 5 In the United States and Europe, it claims the life of one in five men diagnosed with the disease.…”

Section: Introductionmentioning

confidence: 99%

“…5 With extension of the average life span, it has become the most common cancer among males of the Western world accounting for 35% of all cancers. 5 In the United States and Europe, it claims the life of one in five men diagnosed with the disease. 6 Current treatment modalities for localized prostate cancer include surgery and radiation therapy, both of which are associated with risks of nerve damage and sexual and/or bladder dysfunction, and other complications.…”

Section: Introductionmentioning

confidence: 99%

Enhanced therapeutic efficacy of IL-12, but not GM-CSF, expressing oncolytic herpes simplex virus for transgenic mouse derived prostate cancers

et al. 2005

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Replication competent oncolytic herpes simplex viruses (HSV) with broad-spectrum activity against various cancers, including prostate cancer, exert a dual effect by their direct cytocidal action and by eliciting tumor-specific immunity. These viruses can deliver immunoregulatory molecules to tumors so as to enhance the cumulative antitumor response. This is particularly desirable for prostate cancers, which are usually poorly immunogenic. Initial studies described herein comparing the efficacy of three different oncolytic HSVs (G207, G47D, and NV1023) to inhibit the growth of the poorly immunogenic TRAMP-C2 mouse prostate tumors demonstrated that NV1023 was most effective in treating established tumors. The expression of IL-12 on an NV1023 background (NV1042), but not the expression of GM-CSF (NV1034), further enhanced the efficacy of NV1023 in two murine prostate cancer models with highly variable MHC class I levels, Pr14-2 with 91% and TRAMP-C2 with 2% of cells staining. NV1042 also inhibited the growth of distant noninoculated tumors in both prostate cancer models. NV1042 treated tumors exhibited increased immune cell infiltration and decreased levels of angiogenesis. Thus, an IL-12 expressing oncolytic herpes virus, which is capable of direct cytotoxicity and can modulate the otherwise suboptimal immune response through concomitant expression of the cytokine at the site of tumor destruction, could serve as a valuable clinical agent to seek out both overt and occult prostate cancers.

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“…and to 75% by age 80 [5]. With extension of the average life span, it has become the most common cancer among males of the Western world accounting for 35% of all cancers [5].…”

Section: -mentioning

confidence: 99%

“…Systemic toxicity induced by recombinant IL-12 administered systemically or subcutaneously for the treatment of cancer has been a major concern in many prior studies, including phase I and II trials [5][6][7]. In the present study, however, no significant increase in the levels of IL-12 in the serum was observed when measured on days 4, 6, and 10 post-treatments in the TRAMP-C2 unilateral model suggesting that the expression of IL-12 from the NV1 042 virus is a local effect and significant amounts of cytokine is not entering the systemic circulation.…”

mentioning

confidence: 99%

Immunologic Approaches for Oncolytic Viral Therapy of Prostate Cancer

Martuza¹

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and ABSTRACT (Maximum 200 Words)Replication competent oncolytic herpes simplex viruses (HSV) exert a dual effect by their direct cytocidal action and by eliciting tumor specific immunity. These viruses can also deliver immunoregulatory molecules to tumors so as to enhance the cumulative antitumor response. This is particularly desirable for prostate cancers, which are usually poorly immunogenic. In order to generate a cytokine expressing oncolytic virus with enhanced cytotoxicity against prostate cancers and which can stimulate the immune system so as to overcome the immunological complacency observed in prostate cancer patients, we are genetically engineering PC-IL 12 virus using BAC technology from the PC virus, which is an HSV 1 strain selected by screening for enhanced cytotoxicity against prostate cancer cells. The construction is progressing successfully. Additionally, we have described in this report that an IL-12 expressing oncolytic virus (NV 1042) is superior to a GM-CSF expressing virus or a non-cytokine virus in its efficacy against both MHC class I positive (Prl4-2) and negative (TRAMP-C2) mouse prostate tumors. The NV 1042 treated tumors exhibited increased immune cell infiltration and decreased levels of angiogenesis. Thus, an IL-12 expressing oncolytic herpes virus is an effective therapeutic vector against prostate cancers irrespective of their MHC class I status. We initially tested multiple clinical isolates and laboratory strains for replication ability on prostate cancer cells and other cancer cell lines and determined that one lab strain (which we term PC) was consistently the best and was better than strain F, the wild type HSV-1 that our original G207 was derived. DNA from this strain was purified using standard techniques.In order to check the quality of purified viral DNA, the sample was subjected to restriction 4 analysis with Hind Ill. construct will then be available to develop for further constructs as described in the grant application.As noted in the Grant proposal, we will test the recombinant PC viruses in the spontaneously developing prostate cancer mice model, TRAMP. During the submission of the Grant, we had indicated that the TRAMP mice we had established on C57B1/6 strain background did not display the progression of prostate cancer as reported in the literature and therefore we were breeding TRAMP mice on an FVB/N background. We can now report that these mice mimic the progression of pros...

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Increased Incidence of Pathological and Clinical Prostate Cancer With Age: Age Related Alterations of Local Immune Surveillance

Abstract: Apparently, with aging the immune surveillance of the already immune privileged prostate is progressively and further affected. This condition may result in the inability of the gland to eradicate emergent malignant cells.

Cited by 20 publications

References 33 publications

A prostate cancer vaccine comprising whole cells secreting IL-7, effective against subcutaneous challenge, requires local GM-CSF for intra-prostatic efficacy

A prostate cancer vaccine comprising whole cells secreting IL-7, effective against subcutaneous challenge, requires local GM-CSF for intra-prostatic efficacy

Enhanced therapeutic efficacy of IL-12, but not GM-CSF, expressing oncolytic herpes simplex virus for transgenic mouse derived prostate cancers

Immunologic Approaches for Oncolytic Viral Therapy of Prostate Cancer

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