A Randomized, Multicenter, Double-Blind, Phase II Trial of a KLH Conjugated Trivalent Ganglioside Vaccine Containing GM2, GD2 Lactone, and GD3 Lactone With the Immunological Adjuvant OPT-821 Versus OPT-821 Alone in Metastatic Sarcoma Patients Who Are Rendered Disease Free

Sarcoma patients are at high risk for their cancer to recur even when the sarcoma has been removed surgically or treated with radiation or chemotherapy. The patients in the study will be randomized (like flipping a coin) to receive either a vaccine that is combined with an immune system stimulant or the immune system stimulant alone. The immune system stimulant is called OPT-821 and is an immunological booster. The trivalent vaccine is being developed to teach the patient's immune system to recognize 3 types of sugars called GM2, GD2 and GD3 that are found primarily on the surface of sarcoma cells. If the trivalent vaccine can stimulate the patient's immune system to develop antibodies which recognize and target the GM2, GD2 and GM3 sugars, then the patient's antibodies could attack and kill any remaining sarcoma cells potentially preventing the recurrence of sarcoma.

开始日期2010-06-01

申办/合作机构

MabVax Therapeutics, Inc.

100 项与 Sarcoma vaccine(Memorial Sloan-Kettering Cancer Center) 相关的临床结果

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100 项与 Sarcoma vaccine(Memorial Sloan-Kettering Cancer Center) 相关的转化医学

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100 项与 Sarcoma vaccine(Memorial Sloan-Kettering Cancer Center) 相关的专利（医药）

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项与 Sarcoma vaccine(Memorial Sloan-Kettering Cancer Center) 相关的文献（医药）

2022-11-01·European journal of cancer (Oxford, England : 1990)

A randomised phase II trial of a trivalent ganglioside vaccine targeting GM2, GD2 and GD3 combined with immunological adjuvant OPT-821 versus OPT-821 alone in metastatic sarcoma patients rendered disease-free by surgery

Article

作者: Jones, Robin L ; Ryan, Christopher W ; Weiden, Paul ; Agulnik, Mark ; Tap, William D ; Bennett, Cathryn M ; Van Tine, Brian A ; Hansen, David ; George, Suzanne ; Qin, Li-Xuan ; Elias, Anthony D ; Maki, Robert G ; Milhem, Mohammed M ; Hirman, Joe ; D'Angelo, Sandra P ; Schwartz, Gary K ; Carvajal, Richard D ; Budd, G Thomas ; Livingston, Philip O ; Chugh, Rashmi ; Read, William L ; Chmielowski, Bartosz ; Ragupathi, Govind ; Rodler, Eve T ; Rosenbaum, Evan ; Tawbi, Hussein

BACKGROUND:

Recurrence after resection of metastatic sarcoma is common. The gangliosides GM2, GD2 and GD3 are strongly expressed across sarcoma subtypes. We hypothesised that generation of anti-ganglioside antibodies would control micrometastases and improve outcomes in sarcoma patients who were disease-free after metastasectomy.

METHODS:

We conducted a randomised phase II trial of the immunological adjuvant OPT-821 with a KLH-conjugated ganglioside vaccine targeting GM2, GD2 and GD3, versus OPT-821 alone in patients with metastatic sarcoma following complete metastasectomy. Patients received 10 subcutaneous injections at Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68 and 84 and were followed for evidence of recurrent disease. The primary end-point was relapse-free survival. Secondary end-points included overall survival and serologic response.

RESULTS:

A total of 136 patients were randomised, 68 to each arm. The mean age was 51.2, 52.2% were male, 90.4% had relapsed disease, 86.8% had high-grade tumours and 14% had ≥4 metastases resected. Histologies included leiomyosarcoma (33%), spindle cell sarcoma (14%), undifferentiated pleomorphic sarcoma (13%), osteosarcoma (10%), synovial sarcoma (9%), liposarcoma (9%) and others (12%). Most adverse events were Grade ≤2 (83.8% and 70.6% in the vaccine and adjuvant arms, respectively). The most common (≥20% of patients) were injection site reaction (89.7%), fatigue (44.1%) and pyrexia (27.9%) on the vaccine arm, and injection site reaction (69.1%) on the adjuvant only arm. The 1-year relapse-free survival rate (34.5% and 34.8% in the vaccine and OPT-821 monotherapy arm, respectively) did not differ between arms (P = 0.725). One-year overall survival rates were 93.1% and 91.5% in the vaccine and OPT-821 monotherapy arm, respectively (P = 0.578). Serologic responses at week 9 were more frequent on the vaccine arm (96.5% of patients) than in the adjuvant arm (32.8%), and the difference between groups was durable.

CONCLUSIONS:

A sustained serologic response to vaccination was induced with the vaccine, but no difference in recurrence-free or overall survival was observed between treatment arms.

CLINICALTRIALS:

gov identifier: NCT01141491.

2016-03-01·Molecular immunology3区 · 医学

Neem leaf glycoprotein promotes dual generation of central and effector memory CD8 + T cells against sarcoma antigen vaccine to induce protective anti-tumor immunity

3区 · 医学

Article

作者: Sarkar, Madhurima ; Saha, Akata ; Bose, Anamika ; Dasgupta, Shayani ; Bhuniya, Avishek ; Barik, Subhasis ; Guha, Ipsita ; Ghosh, Tithi ; Ghosh, Sarbari ; Baral, Rathindranath

We have previously shown that Neem Leaf Glycoprotein (NLGP) mediates sustained tumor protection by activating host immune response. Now we report that adjuvant help from NLGP predominantly generates CD44(+)CD62L(high)CCR7(high) central memory (TCM; in lymph node) and CD44(+)CD62L(low)CCR7(low) effector memory (TEM; in spleen) CD8(+) T cells of Swiss mice after vaccination with sarcoma antigen (SarAg). Generated TCM and TEM participated either to replenish memory cell pool for sustained disease free states or in rapid tumor eradication respectively. TCM generated after SarAg+NLGP vaccination underwent significant proliferation and IL-2 secretion following SarAg re-stimulation. Furthermore, SarAg+NLGP vaccination helps in greater survival of the memory precursor effector cells at the peak of the effector response and their maintenance as mature memory cells, in comparison to single modality treatment. Such response is corroborated with the reduced phosphorylation of FOXO in the cytosol and increased KLF2 in the nucleus associated with enhanced CD62L, CCR7 expression of lymph node-resident CD8(+) T cells. However, spleen-resident CD8(+) T memory cells show superior efficacy for immediate memory-to-effector cell conversion. The data support in all aspects that SarAg+NLGP demonstrate superiority than SarAg vaccination alone that benefits the host by rapid effector functions whenever required, whereas, central-memory cells are thought to replenish the memory cell pool for ultimate sustained disease free survival till 60 days following post-vaccination tumor inoculation.

2007-10-15·The Journal of infectious diseases2区 · 医学

Efficient Elimination of Multidrug‐ResistantStaphylococcus aureusby Cloned Lysin Derived from Bacteriophage φMR11

2区 · 医学

Article

作者: Mohammad Rashel ; Takako Ujihara ; Jumpei Uchiyama ; Asako Muraoka ; Shigenobu Matsuzaki ; Keiichi Hiramatsu ; Yoshio Uehara ; Shigeyoshi Sugihara ; Ken-Ichi Yagyu ; Motoyuki Sugai ; Shu Kuramoto ; Koichi Honke

We report the successful purification of a cloned lysin encoded by the novel Staphylococcus aureus bacteriophage phi MR11. The lysin, designated MV-L, rapidly and completely lysed cells of a number of S. aureus strains tested, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus and a subset of vancomycin-intermediate S. aureus (VISA) in growing conditions. MV-L-mediated killing is specific to S. aureus and not to other species, except for S. simulans. MV-L exerted its staphylocidal effect synergistically with glycopeptide antibiotics against VISA. MV-L efficiently eliminated MRSA that had been artificially inoculated into the nares of mice. The intraperitoneal administration of MV-L also protected mice against MRSA septic death, without any harmful effects. Although MV-L evoked detectable levels of a humoral response in mice, the antibodies did not abolish the bacteriolytic activity. These results indicate that MV-L might be useful as a powerful therapeutic agent against multidrug-resistant S. aureus infections.

100 项与 Sarcoma vaccine(Memorial Sloan-Kettering Cancer Center) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
尤文肉瘤	临床2期	美国	MabVax Therapeutics, Inc.	2010-06-01
横纹肌肉瘤	临床2期	美国	MabVax Therapeutics, Inc.	2010-06-01
肉瘤	临床2期	-	Memorial Sloan Kettering Cancer Center	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01141491 (CTgov)	临床2期	肉瘤 \| 横纹肌肉瘤 \| 尤文肉瘤	136	OPT-821	糧製網鏇醖獵艱蓋衊鹹(窪廠襯繭簾範齋選蓋選) = 鹹繭鏇衊艱繭鑰窪膚鹹膚遞築顧願齋壓築構鏇 (範鏇願糧鏇憲夢繭製築, 觸壓膚鹽鹹選鬱願壓鹹 ~ 繭廠鑰觸鑰窪衊鑰鏇範) 更多	-	2016-12-07
NCT01141491 (ASCO2014)	临床2期	转移性软组织肉瘤辅助	136	Ganglioside vaccine + OPT821	鑰膚餘網製顧餘觸艱鹽(襯築餘觸衊築糧選衊鹹) = 鹽襯顧繭膚憲顧選襯窪艱鹽範鏇願鹽廠鹽衊膚 (遞選憲廠觸蓋餘繭窪膚 ) 更多	-	2014-05-20
NCT01141491 (ASCO2014)	临床2期	转移性软组织肉瘤辅助	136	Placebo + OPT821	鑰膚餘網製顧餘觸艱鹽(襯築餘觸衊築糧選衊鹹) = 範鬱壓蓋顧鏇遞遞襯膚艱鹽範鏇願鹽廠鹽衊膚 (遞選憲廠觸蓋餘繭窪膚 ) 更多	-	2014-05-20