Cancer anti-angiogenesis vaccines: Is the tumor vasculature antigenically unique?

Wagner, Samuel C.; Ichim, Thomas E.; Ma, Hong; Szymanski, Julia; Perez, Jesus A. Rodriguez; López, Javier; Bogin, Vladimir; Patel, Amit N.; Marincola, Francisco M.; Kesari, Santosh

doi:10.1186/s12967-015-0688-5

Cited by 26 publications

(27 citation statements)

References 115 publications

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“…133,134,153 Destabilization of intratumoral vessel integrity may ensue from dense, overlaying lesional tissue, which can create biomechanical tension and alter blood flow. 133 These tumor-intrinsic microvessels, often detected with mAbs against platelet-endothelial cell adhesion molecule-1 (PECAM-1), generally express low to nil E-selectin, P-selectin, ICAM-1/2, VCAM-1, MadCAM-1, or VAP-1 as has been observed in metastatic melanomas, squamous cell carcinomas (SCCs) and/or tumors of various origin, thereby hindering leukocyte binding, homing and entry into the tumor core.…”

Section: Teff Cell Homing To Solid Primary and Metastatic Tumorsmentioning

confidence: 99%

T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy

Sackstein

Schatton

Barthel

2017

Laboratory Investigation

180

151

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Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively-transferred T effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue. Thus, defects intrinsic to the multi-step T cell homing cascade have become an obvious, though significantly underappreciated contributor to immunotherapy resistance. Conspicuous have been low intralesional frequencies of tumor-infiltrating T-lymphocytes (TILs) below clinically beneficial threshold levels, and peripheral rather than deep lesional TIL infiltration. Therefore, a Teff cell ‘homing deficit’ may arguably represent a dominant factor responsible for ineffective immunotherapeutic outcomes, as tumors resistant to immune-targeted killing thrive in such permissive, immune-vacuous microenvironments. Fortunately, emerging data is shedding light into the diverse mechanisms of immune escape by which tumors restrict Teff cell trafficking and lesional penetrance. In this review, we scrutinize evolving knowledge on the molecular determinants of Teff cell navigation into tumors. By integrating recently described, though sporadic information of pivotal adhesive and chemokine homing signatures within the tumor microenvironment with better established paradigms of T cell trafficking under homeostatic or infectious disease scenarios, we seek to refine currently incomplete models of Teff cell entry into tumor tissue. We further summarize how cancers thwart homing to escape immune-mediated destruction and raise awareness of the potential impact of immune checkpoint blockers on Teff cell homing. Finally, we speculate on innovative therapeutic opportunities for augmenting Teff cell homing capabilities to improve immunotherapy-based tumor eradication in cancer patients, with special focus on malignant melanoma.

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Section: Teff Cell Homing To Solid Primary and Metastatic Tumorsmentioning

confidence: 99%

T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy

Sackstein

Schatton

Barthel

2017

Laboratory Investigation

180

151

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“…Several kinds, compositions, and modes of administration of anti-tumor vaccines have been used with different results [160,161,162,163,164,165,166,167]. More recently, the focus of anti-tumor vaccines has been moved from tumor cells to TME too [7,9,10,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175]. Indeed, the possibility of targeting tumor endothelial cells or the VEGF signaling axis with specific vaccines has been assessed in preclinical studies, and clinical trials are ongoing [168].…”

Section: Msc As Target Cells For Anti-tumor Vaccinesmentioning

confidence: 99%

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi

Giuliani

2016

Vaccines

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The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

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“…Targeting these dividing vascular cells to promote extravasation of the particles into the tumour parenchyma and damage the tumour vasculature is critical for effective use of nanoscale particles since they are unable to effectively penetrate the tumour microenvironment by passive means due to the tumour physiology. Indeed there are several endothelial specific vaccines that are in early stage clinical trials [30], with the goal being to educate the immune system to eradicate the rapidly dividing vasculature within the tumour. Tumour endothelial cells are also under investigation as a target for radiation [31–33] and chemotherapy [34] and we have demonstrated potent therapeutic effects using a vascular targeted gold nanoparticle in recent work [35–38].…”

Section: Introductionmentioning

confidence: 99%

Galectin-1-based tumour-targeting for gold nanostructure-mediated photothermal therapy

Jenkins¹,

Nedosekin

Miller

et al. 2017

International Journal of Hyperthermia

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Purpose To demonstrate delivery of Au nanocages to cells using the galectin-1 binding peptide anginex (Ax) and to demonstrate the value of this targeting for selective in vitro photothermal cell killing. Materials and methods Au nanocages were synthesised, coated with polydopamine (PDA), and conjugated with Ax. Tumour and endothelial cell viability was measured with and without laser irradiation. Photoacoustic (PA) mapping and PA flow cytometry were used to confirm cell targeting in vitro and in tissue slices ex vivo. Results Cell viability was maintained at ≥50% at 100 pM suggesting low toxicity of the nanocage alone. Combining the targeted construct (25 pM) with low power 808 nm laser irradiation for 10–20 min (a duration previously shown to induce rapid and sustained heating of Au nanocages [AuNC] in solution), resulted in over 50% killing of endothelial and tumour cells. In contrast, the untargeted construct combined with laser irradiation resulted in negligible cell killing. We estimate approximately 6 × 104 peptides were conjugated to each nanocage, which also resulted in inhibition of cell migration. Binding of the targeted nanocage reached a plateau after three hours, and cell association was 20-fold higher than non-targeted nanocages both in vitro and ex vivo on tumour tissue slices. A threefold increase in tumour accumulation was observed in preliminary in vivo studies. Conclusions These studies demonstrate Ax’s potential as an effective targeting agent for Au-based theranostics to tumour and endothelial cells, enabling photothermal killing. This platform further suggests potential for multimodal in vivo therapy via next-generation drug-loaded nanocages.

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Cancer anti-angiogenesis vaccines: Is the tumor vasculature antigenically unique?

Cited by 26 publications

References 115 publications

T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy

T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Galectin-1-based tumour-targeting for gold nanostructure-mediated photothermal therapy

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