Unlike conventional ophthalmic OCT, robotically aligning OCT (RAOCT) removes the requirement for close patient/operator proximity and enables remote patient imaging by autonomously aligning itself to the patient while the operator is physically elsewhere. We report kilometer-scale distance between OCT operator and patient and the first robotically aligned OCT angiography images. We acquired remote volumetric RAOCT retinal images from healthy and diseased eyes at the Duke Eye Center on both room-to-room (10m between imager and subject) and between clinic sites(>10km between imager and subject). This can serve as a foundation for socially distanced or telehealth retinal OCT without physically present technicians.
It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse – B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.
P. Jack Hoopes, Courtney Mazur, Bjorn Osterberg, Ailin Song, David Gladstone, Nicole Steinmetz, Frank Veliz, Alicea Bursey, Robert Wagner, Steven Fiering
Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia. Based on the prior experience of our research group including; cancer-based heat therapy, magnetic nanoparticle (mNP) hyperthermia, radiation biology, cancer immunology and Cowpea Mosaic Virus that has been engineered to over express antigenic proteins without RNA or DNA (eCPMV/VLP). This research was designed to determine if and how the intra-tumoral delivery of mNP hyperthermia and VLP can work together to improve local and systemic tumor treatment efficacy. Using the C3H mouse/MTG-B mammary adenocarcinoma cell model and the C57-B6 mouse/B-16-F10 melanoma cancer cell model, our data suggests the appropriate combination of intra-tumoral mNP heat (e.g. 43°C /30-60 minutes) and VLP (100 μg/200 mm3 tumor) not only result in significant primary tumor regression but the creation a systemic immune reaction that has the potential to retard secondary tumor growth (abscopal effect) and resist tumor rechallenge. Molecular data from these experiments suggest treatment based cell damage and immune signals such as Heat Shock Protein (HSP) 70/90, calreticulin, MTA1 and CD47 are potential targets that can be exploited to enhance the local and systemic (abscopal effect) immune potential of hyperthermia cancer treatment
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