The Ursinus Weekly, October 30, 1975

16 U.C. seniors named to Who\u27s who • Prof. presides • U.C. Founder\u27s Day to honor church • Dr. Isaac Asimov named speaker • Editorial: Ursinus\u27 infirmary is ailing! • Letters to the editor: Soccer regrets; Speaking out; Resident vs. day; An open letter to Richard J. Whatley • Newest P.E. prof • Visitor notes strange customs • Renowned sculptor presents project • Forum review: Lisa A. Richette speaks at Ursinus • Ursinus wins! • We\u27re no. 1! • Between inningshttps://digitalcommons.ursinus.edu/weekly/1044/thumbnail.jp

Remodeling of biological tissue: Mechanically induced reorientation of a transversely isotropic chain network

A new class of micromechanically motivated chain network models for soft biological tissues is presented. On the microlevel, it is based on the statistics of long chain molecules. A wormlike chain model is applied to capture the behavior of the collagen microfibrils. On the macrolevel, the network of collagen chains is represented by a transversely isotropic eight chain unit cell introducing one characteristic material axis. Biomechanically induced remodeling is captured by allowing for a continuous reorientation of the predominant unit cell axis driven by a biomechanical stimulus. To this end, we adopt the gradual alignment of the unit cell axis with the direction of maximum principal strain. The evolution of the unit cell axis' orientation is governed by a first-order rate equation. For the temporal discretization of the remodeling rate equation, we suggest an exponential update scheme of Euler-Rodrigues type. For the spatial discretization, a finite element strategy is applied which introduces the current individual cell orientation as an internal variable on the integration point level. Selected model problems are analyzed to illustrate the basic features of the new model. Finally, the presented approach is applied to the biomechanically relevant boundary value problem of an in vitro engineered functional tendon construct.Comment: LaTeX2e, 19 pages, 9 figure

The Ursinus Weekly, November 20, 1975

Sub-stantial lunch presented by Union • Dorm visitation reform urged • The Party\u27s over • Explosive evidence • Student letter sent to Board • New Student Affairs subcommittee formed • Editorial: Communication before tragedy • Letters to the editor: Reactions • Grad. School crunch etc. • ProTheatre puts best foot forward • Coffeehouse reviewed • State of the Union • New service at Myrin • Forum review: Lindsay on energy • Photo exhibit opens • 1-6-1 And something must be done! • Ursinus\u27 women\u27s hockey starlets repeat success! • Wrestler\u27s preview • Manning\u27s men • C. C. team • NBA preview part IIhttps://digitalcommons.ursinus.edu/weekly/1047/thumbnail.jp

The Ursinus Weekly, November 6, 1975

Lloyd joins German Dept. • Parking problems • AAUP speaker discusses Union • Student apprehended • Psych Club news • State of the Union • Hot flicks in Philly • Gurzynski hits century mark • Bearettes tie W. C. • Widener wallops whazoo\u27s woefuls! • Phila. Sixers\u27 hoopla • Here and there • El Espanol vivahttps://digitalcommons.ursinus.edu/weekly/1045/thumbnail.jp

The Ursinus Weekly, October 16, 1975

S.F.A.R.C. reps meet, discuss Library & proctors • Homecoming day is coming • Students, V.P. Richter discuss false alarm • Union plans mini-courses • Library Assoc. to meet at U.C. • New instructor • Editorial: Pride, not prejudice • Letter to the editor: Day vs. resident • Saturday Lunch • Speak up or give up • Freedom of speech • State of the Union • George Allen\u27s Ursinus Redskins • Our captains • Ursinus offense faltershttps://digitalcommons.ursinus.edu/weekly/1043/thumbnail.jp

The Ursinus Weekly, October 2, 1975

Meetings on Perkiomen Valley growth • In memoriam • Gene Shue presents: Year of the Sixers • City planner speaks • Ursinus College appoints Assoc. Prof. of Education • Kane earns Doctorate • Editorial: A different year? • Is there more to life? • New dorms renovated • Saturday Lunch • Forum series opens: Nina Deutsch • Musical notes • Chris Hillman rated • New events at Walnut • Nancy Drew revisited • Alumnus is named to Library post • British history specialist joins Ursinus faculty • Instructor returns to Ursinus • Pa. Dutch Program is success • Instructor appointed to Biology Dept. • Lindback Award presented • Soccer season opens • Ursinus allies with area • Balloons! • Ursinus named a \u2776er • Register now! • Grads elect officers • Yes we can gang didn\u27t • NFC forecast • MAC report • F & M stings Bears 35 - 21https://digitalcommons.ursinus.edu/weekly/1041/thumbnail.jp

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Immunogenicity in humans of a transdermal multipeptide melanoma vaccine administered with or without a TLR7 agonist

Background Experimental cancer vaccines are traditionally administered by injection in subcutaneous tissue or muscle, commonly with adjuvants that create chronic inflammatory depots. Injection of melanoma-derived peptides induces T cell responses; however, the depots that form following injection may inhibit optimization of the immune response. In skin, epidermal Langerhans cells (LC) are a dominant source of professional antigen presenting cells. We hypothesized that: (1) applying melanoma-derived peptides topically, in proximity to LC, could be immunogenic and safe, with low vaccine-site toxicity and (2) topical toll-like receptor 7 (TLR7) agonist would increase immunogenicity of the peptide vaccine.Methods Twelve melanoma peptides plus a tetanus helper peptide were combined with granulocyte macrophage colony stimulating factor (GM-CSF) and were administered topically on days 1, 8, and 15, to 28 patients randomized to one of four adjuvant preparations: (1) incomplete Freund’s adjuvant (IFA); (2) IFA plus a TLR7 agonist (imiquimod) administered on days 0, 7, 14; (3) dimethyl sulfoxide (DMSO) or (4) DMSO+ imiquimod administered on day 0, 7, 14. Every 3 weeks thereafter (x 6), the peptides were combined with GM-CSF and were injected into the dermis and subcutis in an emulsion with IFA. Toxicities were recorded and immune responses assayed by ELIspot.Results CD8+ T cell responses to transdermal vaccination in DMSO occurred in 83% of participants in group 3 and 86% in group 4, and responses to vaccination in IFA were observed in 29% of participants in group 1 and 14% in group 2. Overall, 61% of participants had CD4+ T cell immune responses to the tetanus peptide, with large, durable responses in groups 3 and 4. Five of seven participants in group 4 had a severe rash, one that was dose limiting. Ten-year overall survival was 67% and disease-free survival was 44%.Conclusions These data provide proof of principle for immunogenicity in humans of transdermal immunization using peptides in DMSO. Further study is warranted into the pharmacokinetics and immunobiology of TLR agonists as vaccine adjuvants during transcutaneous application. Overall survival is high, supporting further investigation of this immunization approach