Publications by authors named "Alexandra M Adams"

8 Publications

  • Page 1 of 1

Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma.

Melanoma Res 2021 08;31(4):378-388

Cancer Vaccine Development Program, San Antonio, Texas, USA.

Immunotherapy has revolutionized the treatment of melanoma, yet survival remains poor for patients with metastatic disease. The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe adjuvant therapy for patients with resected stage III/IV melanoma who complete the primary vaccine series. Here, we describe an open-label trial of patients with metastatic melanoma treated with TLPLDC vaccine in addition to standard of care (SoC) therapies. The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles, which are phagocytosed by autologous dendritic cells ex vivo. Patients who recurred while enrolled in a phase IIb trial of adjuvant TLPLDC vaccine (crossover cohort) and patients with measurable metastatic melanoma cohort were offered TLPLDC vaccine along with SoC therapies. Tumor response was measured by RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were estimated by intention-to-treat analysis. Fifty-four patients were enrolled (28 in crossover cohort; 26 in metastatic melanoma cohort). The vaccine was well-tolerated with no grade ≥3 adverse events when given with SoC therapies to include checkpoint inhibitors, BRAF/MEK inhibitors, tyrosine kinase inhibitors, intralesional therapy and/or radiation. In the crossover arm, OS was 76.5% and PFS was 57.1% (median follow-up of 13.9 months). In the metastatic melanoma arm, OS was 85.7% and PFS was 52.2% (median follow-up 8.5 months). The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma.
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http://dx.doi.org/10.1097/CMR.0000000000000758DOI Listing
August 2021

Near Complete Pathologic Response to PD-1 Inhibitor and Radiotherapy in a Patient with Locally Advanced Pancreatic Ductal Adenocarcinoma.

Onco Targets Ther 2021 1;14:3537-3544. Epub 2021 Jun 1.

Department of Surgery, Brooke Army Medical Center, San Antonio, TX, USA.

Pancreatic ductal adenocarcinoma (PDAC) remains deadly despite advances in systemic therapies and surgical techniques. While there is increasing utilization of immune therapies across diverse cancer types, PDAC remains generally resistant to these treatments. We report a case of locally advanced PDAC treated with preoperative radiation and anti-PD-1 immunotherapy guided by preoperative PD-L1 tumor analysis. After 4 months of preoperative therapy, the patient was submitted to resection, demonstrating a near-complete pathologic response on final tumor analysis. We will discuss the relevant literature and current state of immunotherapeutics for PDAC.
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http://dx.doi.org/10.2147/OTT.S311661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179799PMC
June 2021

Safety and efficacy of low-titer O whole blood resuscitation in a civilian level I trauma center.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S162-S168

From the Department of Surgery (P.M.K.B., P.M.M., A.M.A., R.C.C.), Brooke Army Medical Center, Fort Sam Houston, Texas; Uniformed Services University of the Health Sciences (M.E.W.), Bethesda, Maryland; and Department of Trauma and Acute Care Surgery (J.E.F., J.S.R., R.A.H., V.G.S.), Brooke Army Medical Center, Fort Sam Houston, Texas.

Background: Military experience has shown low-titer O whole blood (LTOWB) to be safe and beneficial in the resuscitation of hemorrhaging trauma patients. However, few civilian centers use LTOWB for trauma resuscitation. We evaluated the early experience and safety of a LTOWB program at a level 1 civilian trauma center.

Methods: We retrospectively reviewed our trauma registry from January 2018 to June 2020 for patients admitted in shock (defined as ≥1 of the following: heart rate, >120 beats per minute; systolic blood pressure, <90 mm Hg; or shock index, >0.9) who received blood products within 24 hours. Patients were grouped by resuscitation provided: LTOWB (group 1), component therapy (CT; group 2), and LTOWB-CT (group 3). Safety, outcomes, and variables associated with LTOWB transfusion and mortality were analyzed.

Results: 216 patients were included: 34 in Group 1, 95 in Group 2, and 87 in Group 3. Patientsreceiving LTOWB were more commonly male (p<0.001) and had a penetrating injury (p=0.005). Groups 1 and 3 had higher median ISS scores compared to Group 2 (19 and 20 vs 17; p=0.01). Group 3 received more median units of blood product in the first 4h (p<0.001) and in the first 24h (p<0.001). There was no difference between groups in 24h mortality or transfusion-related complications (all p>0.05). Arrival ED SBP was associated with LTOWB transfusion (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.95-1.00, p=0.03). ED lactate was independently associated with 24h mortality. (OR 1.27, CI 1.02-1.58, p=0.03). LTOWB transfusion was not associated with mortality (p=0.49). Abstract.

Conclusion: Severely injured patients received LTOWB-CT and more overall product units but had similar 24 h mortality when compared with the LTOWB or CT groups. No increase in transfusion-related complications was seen after LTOWB transfusion. Low-titer O whole blood should be strongly considered in the resuscitation of trauma patients at civilian centers.

Level Of Evidence: Retrospective, therapeutic, level IV.
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http://dx.doi.org/10.1097/TA.0000000000003289DOI Listing
August 2021

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis.

Ann Surg Oncol 2021 Feb 27. Epub 2021 Feb 27.

The Angeles Clinic, Santa Monica, CA, USA.

Background: Melanoma therapy has changed dramatically over the last decade with improvements in immunotherapy, yet many patients do not respond to current therapies. This novel vaccine strategy may prime a patient's immune system against their tumor and work synergistically with immunotherapy against advanced-stage melanoma.

Methods: This was a prospective, randomized, double-blind, placebo-controlled, phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine administered to prevent recurrence in patients with resected stage III/IV melanoma. Patients were enrolled and randomized 2:1 to the TLPLDC vaccine or placebo (empty yeast cell wall particles and autologous dendritic cells). Both intention-to-treat (ITT) and per treatment (PT) analyses were predefined, with PT analysis including patients who remained disease-free through the primary vaccine/placebo series (6 months).

Results: A total of 144 patients were randomized (103 vaccine, 41 control). Therapy was well-tolerated with similar toxicity between treatment arms; one patient in each group experienced related serious adverse events. While disease-free survival (DFS) was not different between groups in ITT analysis, in PT analysis the vaccine group showed improved 24-month DFS (62.9% vs. 34.8%, p = 0.041).

Conclusions: This phase IIb trial of TLPLDC vaccine administered to patients with resected stage III/IV melanoma shows TLPLDC is well-tolerated and improves DFS in patients who complete the primary vaccine series. This suggests patients who do not recur early benefit from TLPLDC in preventing future recurrence from melanoma. A phase III trial of TLPLDC + checkpoint inhibitor versus checkpoint inhibitor alone in patients with advanced, surgically resected melanoma is under development.

Trial Registration: NCT02301611.
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http://dx.doi.org/10.1245/s10434-021-09709-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914039PMC
February 2021

AE37: a HER2-targeted vaccine for the prevention of breast cancer recurrence.

Expert Opin Investig Drugs 2021 Jan 3;30(1):5-11. Epub 2020 Dec 3.

Cancer Vaccine Development Program , San Antonio, TX, USA.

Introduction: HER2 is a prevalent growth factor in a variety of malignancies, most prominently breast cancer. Over-expression has been correlated with the poorest overall survival and has been the target of successful therapies such as trastuzumab. AE37 is a novel, HER2-directed vaccine based on the AE36 hybrid peptide (aa776-790), which is derived from the intracellular portion of the HER2 protein, and the core portion of the MHC Class II invariant chain (the Ii-Key peptide). This hybrid peptide is given with GM-CSF immunoadjuvant as the AE37 vaccine.

Areas Covered: This article describes in detail the preclinical science leading to the creation of the AE37 vaccine and examines use of this agent in multiple clinical trials for breast and prostate cancer. The safety profile of AE37 is discussed and opinions on the potential of the vaccine in breast and prostate cancer patient subsets along with other malignancies, are offered.

Expert Opinion: Future trials utilizing the AE37 vaccine to treat other HER2-expressing malignancies are likely to see similar success, and this will be enhanced by combination immunotherapy. Ii-Key modification of other peptides of interest across oncology and virology could yield impressive results over the longer term.
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http://dx.doi.org/10.1080/13543784.2021.1849140DOI Listing
January 2021

In vivo production of psilocybin in E. coli.

Metab Eng 2019 12 21;56:111-119. Epub 2019 Sep 21.

Miami University, Department of Chemical, Paper, And Biomedical Engineering, Oxford, OH, 45056, USA. Electronic address:

Psilocybin, the prodrug of the psychoactive molecule psilocin, has demonstrated promising results in clinical trials for the treatment of addiction, depression, and post-traumatic stress disorder. The development of a psilocybin production platform in a highly engineerable microbe could lead to rapid advances towards the bioproduction of psilocybin for use in ongoing clinical trials. Here, we present the development of a modular biosynthetic production platform in the model microbe, Escherichia coli. Efforts to optimize and improve pathway performance using multiple genetic optimization techniques were evaluated, resulting in a 32-fold improvement in psilocybin titer. Further enhancements to this genetically superior strain were achieved through fermentation optimization, ultimately resulting in a fed-batch fermentation study, with a production titer of 1.16 g/L of psilocybin. This is the highest psilocybin titer achieved to date from a recombinant organism and a significant step towards demonstrating the feasibility of industrial production of biologically-derived psilocybin.
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http://dx.doi.org/10.1016/j.ymben.2019.09.009DOI Listing
December 2019

Cyst Rupture After Endobronchial Ultrasound-guided Transbronchial Needle Aspiration.

J Bronchology Interv Pulmonol 2016 Apr;23(2):e20-2

*New York University Langone Medical Center †Unite Here Medial Center ‡Mount Sinai Beth Israel Medical Center New York, NY.

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http://dx.doi.org/10.1097/LBR.0000000000000277DOI Listing
April 2016
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