analyzing-tumor-tissue-distribution-target-antigen-specific

Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody

Monoclonal antibodies are high affinity multifunctional drugs that work by variable independent mechanisms to eliminate cancer cells. Over the last few ...

University of Virginia

The complement system and B cell complement receptor 2 (CR2), specific for C component C3dg, play important roles in both the innate and adaptive immune response. We used hapten and protein conjugates of anti-CR2 mAbs as models for C3dg-opsonized antigens and immune complexes to examine the handling of and immune response to these reagents in mice and in non-human primates (NHP). Mice immunized and boosted i.v. with only 100 ng of Alexa 488 rat anti-mouse CR1/2 mAb 7G6 had strong IgG immune responses to the Alexa 488 hapten and to rat IgG, compared to very weak immune responses in mice treated with a comparable isotype control; larger doses of Alexa 488 mAb 7G6 did not increase the immune response. A vaccine constructed by cross-linking anthrax protective antigen to mAb 7G6 proved to be effective at low doses in generating sufficiently high titer serum IgG antibodies to neutralize anthrax lethal toxin in vitro and to protect mice from i.v. challenge with anthrax lethal toxin. When biotinylated HB135, a mouse mAb specific for human CR2, was injected i.v. into NHP, the probe manifested the same initial marginal zone B cell binding and subsequent localization to follicular dendritic cells as we have previously reported for comparable experiments in mice. Moreover, i.v. immunization of NHP with 1 microg/kg of Alexa 488 mAb HB135 promoted an IgG immune response to the Alexa 488 hapten and to mouse IgG. Taken together, these results demonstrate the efficacy of using anti-CR2 mAbs as antigen carriers for i.v. immunization with small amounts of antigens without adjuvant.

Low doses of antigen coupled to anti-CR2 mAbs induce rapid and enduring IgG immune responses in mice and in cynomolgus monkeys.

&#x5145;&#x5206;&#x6DB5;&#x76D6;&#x81EA;&#x81A8;&#x5F0F;&#x91D1;&#x5C5E;&#x652F;&#x67B6; (FCSEMS) &#x5DF2;&#x88AB;&#x8BC1;&#x660E;&#x6709;&#x6548;&#x7684;&#x5EFA;&#x7ACB;&#x6076;&#x6027;&#x80C6;&#x9053;&#x6897;&#x963B;&#x3002;&#x6709;&#x5C0F;&#x6570;&#x636E;&#x5206;&#x6790;&#x4ED6;&#x4EEC;&#x6682;&#x65F6;&#x5B89;&#x7F6E;&#x5728;&#x80C6;&#x9053;&#x9ECF;&#x819C;&#x54CD;&#x5E94;&#x3002;

&#x5B8C;&#x5168;&#x6DB5;&#x76D6;&#x81EA;&#x81A8;&#x91D1;&#x5C5E;&#x652F;&#x67B6;&#x6682;&#x65F6;&#x653E;&#x5728;&#x80C6;&#x9053;&#xFF1A; &#x5B89;&#x5168;&#x914D;&#x7F6E;&#x6587;&#x4EF6;&#x548C;&#x7EC4;&#x7EC7;&#x5B66;&#x5206;&#x7C7B;&#x732A;&#x6A21;&#x578B;&#x4E2D;&#x7684;&#x3002;

Fully covered Self-Expanding metal stents (FCSEMS) have been shown efficacious in palliating malignant biliary obstructions. There is little data analyzing mucosal response to their temporary placement in the bile duct.

Fully covered self-expanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model.

Enti&egrave;rement couvert autocoll&eacute; stents en m&eacute;tal (FCSEMS) il a &eacute;t&eacute; d&eacute;montr&eacute;s efficaces pour pallier une obstruction biliaire maligne. Il y a peu de donn&eacute;es analysant la r&eacute;ponse mucosale &agrave; leur placement temporaire dans le canal chol&eacute;doque.

Enti&egrave;rement couvert auto-expansible stents m&eacute;talliques plac&eacute;s temporairement dans le canal chol&eacute;doque : profil d&#39;innocuit&eacute; et de la classification histologique dans un mod&egrave;le porcin.

Vollst&auml;ndig abgedeckt, Self-Expanding, die Metal Stents (FCSEMS) in palliating maligne Lebertumor Hindernisse wirksam erwiesen haben. Sind nur wenige Daten analysieren Schleimhaut-Reaktion auf ihre tempor&auml;re Platzierung in den Gallengang.

Vollst&auml;ndig abgedeckt selbstextrahierende Metal Stents, die vor&uuml;bergehend in den Gallengang gelegt: Sicherheitsprofil und histologische Klassifizierung in einem porcinen Modell.

Completamente coperto ad auto-espansione degli stent metallici (FCSEMS) hanno dimostrati efficaci nell&#39;attenuare le ostruzioni biliari maligne. C&#39;&egrave; poco dati analizzando la risposta della mucosa al loro collocamento temporaneo nel dotto biliare.

Completamente coperto autoespandente stent metallici collocati temporaneamente nel dotto biliare: profilo di sicurezza e classificazione istologica in un modello dei suini.

&#x5B8C;&#x5168;&#x306B;&#x8986;&#x308F;&#x308C;&#x3066;&#x91D1;&#x5C5E;&#x30B9;&#x30C6;&#x30F3;&#x30C8; (FCSEMS) &#x60AA;&#x6027;&#x80C6;&#x9053;&#x969C;&#x5BB3;&#x7269;&#x306E; palliating &#x306E;&#x52B9;&#x679C;&#x304C;&#x793A;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B; Self-Expanding&#x3002;&#x7C98;&#x819C;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x80C6;&#x7BA1;&#x5185;&#x306E;&#x4E00;&#x6642;&#x7684;&#x306A;&#x914D;&#x7F6E;&#x306E;&#x5206;&#x6790;&#x30C7;&#x30FC;&#x30BF;&#x304C;&#x307B;&#x3068;&#x3093;&#x3069; &#x3057;&#x307E;&#x3059;&#x3002;

&#x80C6;&#x7BA1;&#x5185;&#x306B;&#x4E00;&#x6642;&#x7684;&#x306B;&#x914D;&#x7F6E;&#x3055;&#x308C;&#x308B;&#x81EA;&#x5DF1;&#x5C55;&#x958B;&#x578B;&#x306E;&#x91D1;&#x5C5E;&#x30B9;&#x30C6;&#x30F3;&#x30C8;&#x3092;&#x5B8C;&#x5168;&#x306B;&#x30AB;&#x30D0;&#x30FC;&#xFF1A; &#x5B89;&#x5168;&#x6027;&#x30D7;&#x30ED;&#x30D5;&#x30A1;&#x30A4;&#x30EB;&#x3068;&#x8C5A;&#x306E;&#x30E2;&#x30C7;&#x30EB;&#x306B;&#x304A;&#x3051;&#x308B;&#x7D44;&#x7E54;&#x5B66;&#x7684;&#x5206;&#x985E;&#x3002;

&#xC644;&#xC804; &#xAE08;&#xC18D; &#xC2A4;&#xD150; (FCSEMS) &#xD2B8; palliating &#xC545;&#xC131; &#xB2F4; &#xC999;&#xC758; &#xC7A5;&#xC560;&#xBB3C;&#xC5D0; &#xD6A8;&#xB2A5; &#xD45C;&#xC2DC; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4; Self-Expanding &#xB36E;&#xC5EC; &#xC788;&#xB2E4;. &#xB2F4; &#xAD00;&#xC5D0; &#xC784;&#xC2DC; &#xC704;&#xCE58;&#xB97C; &#xC810; &#xB9C9; &#xC751;&#xB2F5;&#xC744; &#xBD84;&#xC11D; &#xD558;&#xB294; &#xC791;&#xC740; &#xB370;&#xC774;&#xD130;&#xC785;&#xB2C8;&#xB2E4;.

&#xC644;&#xC804;&#xD788; &#xB2F4; &#xAD00;&#xC5D0; &#xC784;&#xC2DC;&#xB85C; &#xBC30;&#xCE58; &#xC790;&#xCCB4; &#xAE08;&#xC18D; &#xC2A4;&#xD150; &#xD2B8;&#xB97C; &#xD3EC;&#xD568;: &#xC548;&#xC804; &#xD504;&#xB85C;&#xD544;&#xACFC; &#xB3FC;&#xC9C0; &#xBAA8;&#xB378;&#xC5D0;&#xC11C; &#xC870;&#xC9C1;&#xD559; &#xBD84;&#xB958;.

Totalmente cubierto autoexpandible stents met&aacute;licos (FCSEMS) se han demostrado eficaces para paliar la obstrucci&oacute;n biliar maligna. Hay pocos datos, analizar la mucosa ante su colocaci&oacute;n temporal en la v&iacute;a biliar.

La cobertura completa de metal autoexpandible colocados temporalmente en el conducto biliar: Perfil de seguridad y clasificaci&oacute;n histol&oacute;gica en un modelo porcino.

Backgrounds. Limited effective palliative treatments exist for pancreatic cancer which includes surgery or chemotherapy. Radiofrequency ablation (RFA) uses high frequency alternating current to ablate diseased tissue and has been used to treat various tumors. In this study, we evaluated a prototype probe adjusted to the EUS-needle to perform EUS-RFA to permit coagulative necrosis in the pancreas. Methods. Five Yucatan pigs underwent EUS-guided radiofrequency ablation of the head of their pancreas. Using an EUS-needle, RFA was applied with 6 mm and then 10 mm of the probe exposed at specific wattage for preset durations. Results. Only one pig showed moderate levels of pancreatitis (20% proximal pancreatitis). The other animals showed much lower areas of tissue damage. In 3 of the 5 pigs, the proximal pancreas showed greater levels of tissue injury than the distal pancreas, consistent with the proximity of the tissue to the procedure site. In 1 pig, both proximal and distal pancreas showed minimal pancreatitis (1%). There was minimal evidence of fat necrosis in intra-pancreatic and/or extra-pancreatic adipose tissue. Conclusion. EUS-guided RFA of the pancreatic head with the monopolar probe through a 19-gauge needle was well tolerated in 5 Yucatan pigs and with minimal amount of pancreatitis.

Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of the Pancreas in a Porcine Model.

OBJECTIVE Ultrasound can be precisely focused through the intact human skull to target deep regions of the brain for stereotactic ablations. Acoustic energy at much lower intensities is capable of both exciting and inhibiting neural tissues without causing tissue heating or damage. The objective of this study was to demonstrate the effects of low-intensity focused ultrasound (LIFU) for neuromodulation and selective mapping in the thalamus of a large-brain animal. METHODS Ten Yorkshire swine ( Sus scrofa domesticus) were used in this study. In the first neuromodulation experiment, the lemniscal sensory thalamus was stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs) were monitored. In a second mapping experiment, the ventromedial and ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU, while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the acoustic focus was assessed using MR thermography. At the end of the experiments, all tissues were assessed histologically for damage. RESULTS LIFU targeted to the ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% ± 11.4% (mean ± SD) compared with baseline recordings. Second, we found a similar degree of inhibition with a high spatial resolution (∼ 2 mm) since adjacent thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus could be inhibited without affecting the ventrolateral nucleus. During MR thermography imaging, there was no observed tissue heating during LIFU sonications and no histological evidence of tissue damage. CONCLUSIONS These results suggest that LIFU can be safely used to modulate neuronal circuits in the central nervous system and that noninvasive brain mapping with focused ultrasound may be feasible in humans.

Article	Year
Low doses of antigen coupled to anti-CR2 mAbs induce rapid and enduring IgG immune responses in mice and in cynomolgus monkeys. Molecular immunology\| PubMed ID: 16631928	2007
Fully covered self-expanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model. BMC gastroenterology\| PubMed ID: 21689439	2011
Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of the Pancreas in a Porcine Model. Gastroenterology research and practice\| PubMed ID: 23049547	2012
Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound. Journal of neurosurgery\| PubMed ID: 28430035	2018

Jeremy Gatesman

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