Phase I Trial of ImmTher, a New Liposome-Incorporated Lipophilic Disaccharide Tripeptide

Vosika, Gerald J.; Cornelius, Dennis A.; Gilbert, Carl W.; Sadlik, John R.; Bennek, John A.; Doyle, Anne; Hertsgaard, Doris

doi:10.1097/00002371-199108000-00004

Cited by 25 publications

(10 citation statements)

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“…They are natural components of the lung surfactant and both PC and PG have been used in clinical trials involving intravenous injections of liposomes. (24)(25)(26) The fatty acid palmitic acid is a fully saturated compound less prone to peroxidation or degradation. Large unilamellar liposomes which have a high encapsulation efficiency thus limiting the amount of lipid required, (29) have been administered systemically in patients.…”

Section: Discussionmentioning

confidence: 99%

Systemic Toxicology and Laser Safety of Laser Targeted Angiography with Heat Sensitive Liposomes

Asrani

D’Anna

Alkan-Önyüksel³

et al. 1995

Journal of Ocular Pharmacology and Therapeutics

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Angiography is currently limited by its lack of local and tissue specificity. The dye rapidly fills both the retinal and choroidal vessels and leaks out of the vessels thus hampering visualization of small vascular beds such as occult choroidal neovascularization. We have developed a method of laser targeted delivery based on encapsulating the dye in heat sensitive liposomes, administering the liposomes intravenously and causing them to release their content by noninvasively warming the target tissue with a laser pulse delivered through the pupil. The local release yields a bright fluorescent bolus which selectively highlights retinal or choroidal vessels. A preliminary investigation of the potential side effects of the method is presented. In rats the systemic toxicity of carboxyfluorescein-entrapped liposomes was compared with that of the free dye. No significant difference was found between the two. Non-human primates exposed to repeated laser targeted angiography were monitored over time and no significant side effects were observed. The safety of the laser exposures was assessed by conventional fluorescein angiography and histopathology. Choroidal laser targeted angiography was achieved without damage. Retinal laser targeted angiography was accompanied by mild and local damage in an area remote from the fovea. The study indicates that laser targeted choroidal angiography can be performed safely and holds promise for diseases such as age related macular degeneration with occult choroidal neovascularization. Further improvements are needed to ensure that no side effects accompany retinal laser targeted angiography.

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Section: Discussionmentioning

confidence: 99%

Systemic Toxicology and Laser Safety of Laser Targeted Angiography with Heat Sensitive Liposomes

Asrani

D’Anna

Alkan-Önyüksel³

et al. 1995

Journal of Ocular Pharmacology and Therapeutics

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“…N ‐acetylglucosaminyl‐ N ‐acetylmuramyl‐ l ‐Ala‐ d ‐isoGlu‐ l ‐Ala‐GDP also known as DTP‐GDP ( 20 ) is a lipophilic liposome‐encapsulated disaccharide tripeptide derivative of MDP (known under the brand name ImmTher) and a potent inducer of monocyte‐mediated cytotoxicity in vitro and in vivo . For example, in vitro study of Worth et al showed that 20 activated human monocytes to produce inflammatory cytokines (TNF‐α, IL‐1, IL‐6, IL‐8, IL‐12, macrophage chemotactic, and activating factor) and inhibit the growth of several human cell lines including Ewing's sarcoma (RD‐ES, SK‐ES‐1, and A4573‐EWS), osteosarcoma (SAOS‐2, MG‐63, and TE‐85), and melanoma (A375).…”

Section: Nod Ligands As Anticancer Agentsmentioning

confidence: 99%

“…Toxic effects occurred at doses greater than 0.8 mg/m 2 and included fever, chills, and hypotension. More importantly, ImmTher caused a regression of lung and liver metastases in three patients with metastatic colon carcinoma . Due to the promising anticancer activity observed in preclinical and phase I clinical study ImmTher entered phase II clinical study to assess the 2‐year disease‐free survival of patients with high‐risk Ewing's sarcoma receiving vincristine, DOX, CTX, and dexrazoxane in the presence or absence of 20 .…”

Section: Nod Ligands As Anticancer Agentsmentioning

confidence: 99%

Harnessing the untapped potential of nucleotide‐binding oligomerization domain ligands for cancer immunotherapy

Nabergoj

Mlinarič-Raščan

Jakopin

2018

Medicinal Research Reviews

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In the last decade, cancer immunotherapy has emerged as an effective alternative to traditional therapies such as chemotherapy and radiation. In contrast to the latter, cancer immunotherapy has the potential to distinguish between cancer and healthy cells, and thus to avoid severe and intolerable side‐effects, since the cancer cells are effectively eliminated by stimulated immune cells. The cytosolic nucleotide‐binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are important components of the innate immune system and constitute interesting targets in terms of strengthening the immune response against cancer cells. Many NOD ligands have been synthesized, in particular NOD2 agonists that exhibit favorable immunostimulatory and anticancer activity. Among them, mifamurtide has already been approved in Europe by the European Medicine Agency for treating patients with osteosarcoma in combination with chemotherapy after complete surgical removal of the primary tumor. This review is focused on NOD receptors as promising targets in cancer immunotherapy as well as summarizing current knowledge of the various NOD ligands exhibiting antitumor and even antimetastatic activity in vitro and in vivo.

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“…For example, N -acetylglucosaminyl- N -acetylmuramyl- l -Ala- d -isoGlu- l -Ala-glyceroldipalmitate (DTP-GDP) is a potent macrophage activator, and when formulated as adjuvant in liposomes, induced remission in human metastatic colorectal cancer and enhanced both humoral and cellular immunity. Similar to MDP, it induced high secretion of TNF-α, IL-1 and IL-6, and shared MDP’s toxicity, producing fever, chills and hypotension at high doses (>0.8 mg/m 2 ) [88,89]. …”

Section: Mycobacterial Carbohydrate Adjuvant Compoundsmentioning

confidence: 99%

Carbohydrate-based immune adjuvants

Petrovsky

Cooper

2011

Expert Review of Vaccines

136

102

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The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage.

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Phase I Trial of ImmTher, a New Liposome-Incorporated Lipophilic Disaccharide Tripeptide

Cited by 25 publications

References 0 publications

Systemic Toxicology and Laser Safety of Laser Targeted Angiography with Heat Sensitive Liposomes

Systemic Toxicology and Laser Safety of Laser Targeted Angiography with Heat Sensitive Liposomes

Harnessing the untapped potential of nucleotide‐binding oligomerization domain ligands for cancer immunotherapy

Carbohydrate-based immune adjuvants

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