Therapeutic/prophylactic agent for prostate cancer
Inventors
Kaneda, Yasufumi • Kawaguchi, Yoshifumi • Itai, Toshimitsu
Assignees
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Publication Number
US-8691212-B2
Publication Date
2014-04-08
Expiration Date
Abstract
Provided are a novel therapeutic agent and therapeutic method for prostatic cancers. More specifically, a prostatic cancer therapeutic/prophylactic agent having a viral envelope vector, particularly a Sendai viral envelope vector, as an active ingredient, the therapeutic/prophylactic agent which is an apoptosis induction promoter, the therapeutic/prophylactic agent used for prostatic cancers whose androgen susceptibility has been partially or completely reduced, and a melanoma therapeutic/prophylactic agent containing a Sendai viral envelope vector as the only active ingredient, and the like are provided.
Core Innovation
The invention relates to a pharmaceutical therapeutic/prophylactic agent for prostatic cancer and melanoma in which a viral envelope, particularly an inactivated Sendai (HVJ-E) envelope, is the active ingredient. The agent is described as targeting prostatic cancers with reduced androgen susceptibility, including hormone-refractory disease, and it is proposed to induce tumor apoptosis.
The described mechanism includes adhesion/fusion mediated effects, induction of interferon-α/β (type I interferons), activation of the JAK-STAT pathway, and engagement of RIG-I, followed by caspase activation and activation of NK cells and CTLs. The document further links these effects to tumor regression outcomes and immune activation consistent with the proposed apoptotic and interferon-related pathways.
For prostatic cancer with reduced androgen susceptibility after endocrine therapy, the document states administration of an effective amount of a viral envelope (wild-type Sendai virus envelope and related forms such as inactivated preparations) to an individual in need thereof. The partial content reports in vivo regression of hormone-refractory PC3 tumors in SCID mice, and it also reports melanoma (B16/BL6) tumor suppression and a survival benefit at low HVJ-E doses.
Claims Coverage
The independent claim set includes one independent method claim with multiple dependent refinements, yielding several inventive feature variations. Across the claim family, the main inventive features center on using a Sendai virus envelope to treat prostatic cancer in individuals with endocrine-therapy history and reduced androgen susceptibility, with dependent claims refining the viral-envelope form and patient/cancer status (e.g., hormone-refractory and GD1a expression).
Endocrine-therapy history and reduced androgen susceptibility prostatic cancer treatment with wild-type Sendai virus envelope
Administering to an individual in need thereof an effective amount of a wild-type Sendai virus envelope to a prostatic cancer patient having a history of receiving endocrine therapy and bearing a prostatic cancer whose androgen susceptibility has been partially or completely reduced.
Wild-type Sendai virus envelope form as inactivated wild-type Sendai virus envelope-derived preparation
Administering a wild-type Sendai virus envelope that is derived from an inactivated wild-type Sendai virus envelope.
Direct administration by direct injection into the prostatic cancer
Directly injecting the viral envelope into prostatic cancer.
Hormone-refractory prostatic cancer after endocrine therapy
Treating a prostatic cancer patient with a history of receiving endocrine therapy wherein the prostatic cancer is hormone-refractory.
GD1a-expressing hormone-refractory prostatic cancer
Treating hormone-refractory prostatic cancer that expresses GD1a.
Overall, the claim coverage focuses on treating prostatic cancer in patients with endocrine-therapy history and partially or completely reduced androgen susceptibility by administering an effective amount of a Sendai virus envelope, with refinements specifying inactivated wild-type-derived envelope preparations, direct injection, hormone-refractory status, and optionally GD1a expression.
Stated Advantages
Reduces tumor burden with reported in vivo regression of hormone-refractory PC3 tumors in SCID mice.
Suppresses melanoma tumor growth (B16/BL6) and provides survival benefit at low HVJ-E doses.
Induces tumor apoptosis associated with interferon-α/β induction, JAK-STAT activation, RIG-I engagement, caspase activation, and NK-cell/CTL activation.
Reportedly achieves reduced immunotoxicity versus conventional chemo [as stated in the partial content].
Documented Applications
Treating prostatic cancer in individuals with a history of receiving endocrine therapy, including cases with partially or completely reduced androgen susceptibility (including hormone-refractory disease).
Treating melanoma, with reported tumor suppression and survival benefit in the cited melanoma model (B16/BL6) in the partial content.
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