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Intra-arterial Versus Intravenous Adoptive Cell Therapy in a Mouse Tumor Model.

ABSTRACT: Adoptive cell transfer therapy for cancer has existed for decades and is experiencing a resurgence in popularity that has been facilitated by improved methods of production, techniques for genetic modification, and host preconditioning. The trafficking of adoptively transferred lymphocytes and infiltration into the tumor microenvironment is sine qua non for successful tumor eradication; however, the paradox of extremely poor trafficking of lymphocytes into the tumor microenvironment raises the issue of how best to deliver these cells to optimize entry into tumor tissue. We examined the route of administration as a potential modifier of both trafficking and antitumor efficacy. Femoral artery cannulation and tail vein injection for the intra-arterial (IA) and IV delivery, respectively, were utilized in the B16-OVA/OT-I mouse model system. Both IV and IA infusions showed decreased tumor growth and prolonged survival. However, although significantly increased T-cell tumor infiltration was observed in IA mice, tumor growth and survival were not improved as compared with IV mice. These studies suggest that IA administration produces increased early lymphocyte trafficking, but a discernable survival benefit was not seen in the murine model examined.

SUBMITTER: Visioni A

PROVIDER: S-EPMC6092084 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Intra-arterial Versus Intravenous Adoptive Cell Therapy in a Mouse Tumor Model.

Visioni Anthony A Kim Minhyung M Wilfong Chandler C Blum Asher A Powers Colin C Fisher Daniel D Gabriel Emmanuel E Skitzki Joseph J

Journal of immunotherapy (Hagerstown, Md. : 1997) 20180901 7

Adoptive cell transfer therapy for cancer has existed for decades and is experiencing a resurgence in popularity that has been facilitated by improved methods of production, techniques for genetic modification, and host preconditioning. The trafficking of adoptively transferred lymphocytes and infiltration into the tumor microenvironment is sine qua non for successful tumor eradication; however, the paradox of extremely poor trafficking of lymphocytes into the tumor microenvironment raises the i ...[more]

PMID: 29985207

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Project description:Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.

Project description:OBJECTIVE:The aim of this study was to compare the risk of hypersensitivity reactions to iopromide after intra-arterial (IA) administration and intravenous (IV) administration. MATERIALS AND METHODS:Four observational studies were pooled. Almost half of the study population (48.1%) was from Europe, and one quarter each from China (27.6%) and other Asia countries (24.1%). All patients received iopromide either intra-arterially or intravenously for angiographic procedures (mostly cardio-angiography) or contrast-enhanced computed tomography. A nested case-control analysis, including a multivariable logistic regression model, was performed. Cases were defined by patients with a typical and unequivocal hypersensitivity (assumed non-IgE-mediated) reaction; controls were patients without any recorded reaction. The primary target variable is the odds ratio of having a hypersensitivity reaction after IA versus IV administration. RESULTS:A total of 133,331 patients met the inclusion criteria, 105,460 and 27,871 patients received iopromide IV or IA, respectively. Hypersensitivity reactions were recorded for 822 patients, and 132,509 patients served as controls.Major risk factors for hypersensitivity reactions were method of injection (IV vs IA), age (18 to <50 years vs ?65 years), history of allergy or previous contrast media reaction (all P < 0.001), and asthma (P = 0.005).A total of 766 patients (0.7%) and 56 patients (0.2%) were recorded with hypersensitivity reactions after IV or IA administration, respectively (P < 0.0001).Adjusted odds ratio (IA vs IV) was 0.23 (95% confidence interval, 0.16-0.32) for all countries together: for China only, 0.22 (0.11-0.44); for all countries without China, 0.36 (0.25-0.53).Most frequent reactions were erythema/urticaria/rash, pruritus, and cough/sneezing. CONCLUSIONS:Hypersensitivity reactions to iopromide were significantly less frequently recorded after IA administrations. This could be related to the delayed and diluted arrival of iopromide to the lungs.

Dataset Information

Intra-arterial Versus Intravenous Adoptive Cell Therapy in a Mouse Tumor Model.

Publications

Intra-arterial Versus Intravenous Adoptive Cell Therapy in a Mouse Tumor Model.

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