Archaeosome Adjuvant Overcomes Tolerance to Tumor‐Associated Melanoma Antigens Inducing Protective CD8<sup>+</sup> T Cell Responses

Krishnan, Lakshmi; Deschatelets, Lise; Stark, Felicity C.; Gurnani, Komal; Sprott, G. Dennis

doi:10.1155/2010/578432

Cited by 32 publications

(37 citation statements)

References 54 publications

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“…8 These bipolar lipids, which are also called bolalipids or bolaamphiphiles, 9 are of great interest for applications in biotechnology, pharmaceuticals, and materials science. 10−15 Liposomes composed of such bipolar lipids are sometimes called archaeosomes 16 and are suitable as long-circulating vehicles for drug-delivery purposes. 17−19 However, the isolation of these lipids from natural sources is extremely expensive and leads to mixtures with respect to a variety of alkyl chain structures found in the natural extracts.…”

Section: ■ Introductionmentioning

confidence: 99%

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

et al. 2015

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In the present work, we describe the synthesis and temperature-dependent aggregation behavior of two examples of a new class of highly asymmetrical glycerol diether bolaphospholipids. The bolalipids contain a long alkyl chain (C32) bound to glycerol in the sn-3 position, carrying a hydroxyl group at the ω position. The C16 alkyl chain in the sn-2 position either possesses a racemic methyl branch at the 10 position of the short alkyl chain (lipid II) or does not (lipid I). The sn-1 position of the glycerol is linked to a zwitterionic phosphocholine moiety. The temperature-dependent aggregation behavior of both bolalipids was studied using differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and X-ray scattering. Aggregate structures were visualized by transmission electron microscopy (TEM). We show that both bolalipids self-assemble into large lamellar sheetlike aggregates. Closed lipid vesicles or other aggregate structures such as tubes or nanofibers, as usually found for diglycerol tetraether lipids, were not observed. Within the lamellae the bolalipid molecules are arranged in an antiparallel (interdigitated) orientation. Lipid I, without an additional methyl moiety in the short alkyl chain, shows a lamellar phase with high crystallinity up to a temperature of 34 °C, which was not observed before for other phospholipids.

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Section: ■ Introductionmentioning

confidence: 99%

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

et al. 2015

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“…128 Archaeosome have been shown to overcome immunologic tolerance to melanoma self antigens and effectively evoke CD8 C T cells. 129 The use of mAbs, Ab fragments (Fab, single chain variable fragment, scFv) and single domain antibodies, (sdAbs) can also act as highly specific probes when they are attached to NPs to aid in targeted delivery of various antitumor cytotoxic agents. 130,131 Therefore, overall combinatorial approaches including antibody targeting, chemotherapy and immunotherapy are growing in popularity due to their ability to combine specific targeting to cancer cells and potent antitumor effects.…”

Section: Combination Therapymentioning

confidence: 99%

Potential applications of nanoparticles in cancer immunotherapy

Jia

Omri

Krishnan

et al. 2016

Human Vaccines & Immunotherapeutics

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In recent years considerable progress has been made in the field of cancer immunotherapy whereby treatments that modulate the body's own immune system are used to combat cancer. This has the potential to not only elicit strong anti-cancer immune responses which can break pre-existing tolerance and help promote tumor regression, but could also induce immunological memory which may help prevent tumor recurrence. In order to ensure effective delivery of immunotherapeutic agents, such as vaccines, checkpoint inhibitors, chemotherapeutic agents and nucleic acids, a safe and effective delivery system is often required. One such approach is the use of multifunctional nanoparticles (NPs), such as liposomes, polymers, micelles, dendrimers, inorganic NPs, and hybrid NPs, which have the potential to combine the delivery of a diverse range of therapeutic immunomodulators thereby increasing the efficacy of tumor cell killing. This review focuses on recent progress in NP-mediated immunotherapy for the treatment of cancer.

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“…Cancer vaccines have been studied for several decades and are intended either to prevent the development of cancer or to treat existing cancers (22)(23)(24). However, advances in this field have been slower than those in other forms of immunotherapy (24)(25)(26). In order to overcome the poor immunogenicity of tumors, administration of tumor antigens with an effective adjuvant is theoretically a good strategy.…”

Section: Improved Antitumor Effects In B16 Lysate Plus Poly I:c Vaccimentioning

confidence: 99%

B16 cell lysates plus polyinosinic-cytidylic acid effectively eradicate melanoma in a mouse model by acting as a prophylactic vaccine

Lin

Zhao

Fan

et al. 2014

Molecular Medicine Reports

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Abstract. Th1 antigen-specific T cells secrete interferon-γ, which is able to kill antigen-specific cancer cells and is helpful for cancer vaccines. The aim of the present study was to explore whether B16 cell lysates plus polyinosinic-cytidylic acid (poly I:C) can effectively inhibit the progression of melanoma in an animal model. In the present study, C57BL/6 mice were divided into three groups, with each group containing more than six mice. The groups of mice were immunized twice with B16 cell lysates plus poly I:C, B16 cell lysates, or phosphate-buffered saline only, respectively. The in vivo results demonstrated that splenocytes from the mice immunized with B16 cell lysates plus poly I:C contained higher percentages of CD3 + CD8 + T lymphocytes and CD3 + CD4 + T lymphocytes, which were detected by a fluorescence-activated cell sorter, and produced higher levels of antigen-specific splenocyte proliferation activity, as detected by MTT assay. The splenocytes from the mice immunized with B16 cell lysates in combination with poly I:C produced higher levels of interferon-γ, as detected by quantitative polymerase chain reaction and ELISA, as well as cytotoxic T lymphocyte activity when stimulated in vitro with B16 lysates. Additionally, subcutaneous immunization of the C57BL/6 mice with B16 cell lysates plus poly I:C conferred greater protection against tumor-forming B16 melanoma cells than that of the mice immunized with injection of B16 cell lysate alone. In conclusion, the cancer vaccine of B16 cell lysates plus poly I:C exerts potently protective effects that polarize responses toward Th1 and elicit antitumor immunity. IntroductionMalignant melanoma is a serious disease arising from melanocytes which threatens human health in China and worldwide (1,2). The incidence and mortality rate of malignant melanoma continues to increase at a higher rate than that of any other type of malignancy (3,4). Although melanoma is curable if detected at an early localized stage, metastatic malignant melanoma has already become a therapeutic challenge (5). Hundreds of patients with advanced stage III or IV melanoma, particularly those with metastatic disease, have participated in studies of immunological therapy having failed on chemotherapy (6). Thus, ways to prevent and treat malignant melanoma using immunological methods are urgently required. Vaccination has been used for centuries, causing mortality due to infectious disease in humans to profoundly decrease, but a number of serious global diseases with no effective vaccines remain, including acquired immunodeficiency syndrome, influenza, malaria and cancer. It is harder to produce effective immune responses when using vaccines as a treatment for cancer, compared with when using preventive cancer vaccines (7,8). The cancer vaccine for cervical tumors is the first vaccine to prevent human cancer. With the success of the cervical cancer vaccine, an increasing number of researchers have been working to identify novel and effective cancer vaccines. Thus, the aim of the present ...

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Archaeosome Adjuvant Overcomes Tolerance to Tumor‐Associated Melanoma Antigens Inducing Protective CD8⁺ T Cell Responses

Cited by 32 publications

References 54 publications

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

Potential applications of nanoparticles in cancer immunotherapy

B16 cell lysates plus polyinosinic-cytidylic acid effectively eradicate melanoma in a mouse model by acting as a prophylactic vaccine

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Archaeosome Adjuvant Overcomes Tolerance to Tumor‐Associated Melanoma Antigens Inducing Protective CD8+ T Cell Responses

Cited by 32 publications

References 54 publications

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

Highly Asymmetrical Glycerol Diether Bolalipids: Synthesis and Temperature-Dependent Aggregation Behavior

Potential applications of nanoparticles in cancer immunotherapy

B16 cell lysates plus polyinosinic-cytidylic acid effectively eradicate melanoma in a mouse model by acting as a prophylactic vaccine

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Archaeosome Adjuvant Overcomes Tolerance to Tumor‐Associated Melanoma Antigens Inducing Protective CD8⁺ T Cell Responses