Tumor Lysate, Particle-loaded, Dendritic Cell Research Articles

Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is made by ex vivo priming matured autologous dendritic cells (DCs) with yeast cell wall particles (YCWPs) loaded with autologous tumor lysate...

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

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.

The influence of harvest method on dendritic cell function and clinical outcomes in a randomized trial of a dendritic cell vaccine to prevent recurrences in high-risk melanoma.

9548 Background: A randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine was conducted to prevent recurrence in patients (pts) with resected stage III/IV melanoma. Two methods for dendritic cell (DC) harvest were used for vaccine production, including no pretreatment or pretreatment with granulocyte-colony stimulating factor (G-CSF) in an attempt to reduce blood draw volumes. This analysis investigates differences in clinical outcomes and RNA gene expression between these DC harvest methods for TLPLDC vaccine creation. Methods: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles (YCWPs) and exposing them to phagocytosis by DCs. By investigator/pt choice, pts had 120mL of blood drawn for DC harvest, or pts received 300μg of G-CSF for pre-DC mobilization and a 50-70 mL blood draw 24-48 hours later. Total vaccine production time was 72 hrs. Pts were randomized 2:1 to receive TLPLDC or placebo (DCs exposed to empty YCWPs). 1-1.5 x10^6 cells/dose were injected intradermally at 0, 1, 2, 6, 12, and 18 months. Differences in disease free survival (DFS) and overall survival (OS) were evaluated by Kaplan Meier analysis between pts who did not receive pretreatment (TLPLDC), pts who did receive pretreatment with G-CSF (TLPLDC+G), and pts receiving placebo. RNA-seq analysis was performed on the total RNA of pts’ prepared TLPLDC vaccines to assess gene expression. Relative RNA expression (RRE) was compared between TLPLDC and TLPLDC+G. Results: As previously reported, 144 pts were randomized: 103 received TLPLDC (46 TLPLDC, 57 TLPLDC+G) and 41 received placebo. There were no significant clinicopathologic or treatment differences between the three treatment arms. Survival was significantly improved in TLPLDC compared to TLPLDC+G or placebo, including 36-month OS (92.9% vs 62.8% vs 72.3% respectively, p = 0.022) and DFS (51.8% vs 23.4% vs 27.1%, p = 0.027). When compared to TLPLDC+G (n = 3) vaccine, RNA-seq from TLPLDC vaccine (n = 3) showed upregulation of genes associated with DC maturation, including HLA-DMB (RRE: 3.60), IFIT1 (3.38), CD27 (3.26), IFI44L (3.24), MX1 (2.96), HLA-DQA1 (2.67), HLA-DRA (2.40), CD49D (2.34) and CD74 (2.09), while downregulated genes were associated with DC suppression or immaturity including SERPINA1 (RRE:7.8), TLR2 (6.65), CCR1 (5.11), IL10 (4.19), CD93 (3.84) and CD14 (3.25). Conclusions: Pts receiving TLPLDC vaccine had significantly improved OS and DFS, while outcomes remained similar between those who received TLPLDC+G vs placebo. Pts who did not receive G-CSF had higher expression of genes linked to DC maturation and antigen processing and presentation, likely explaining the improvement in clinical efficacy. A phase III trial to further assess the TLPLDC vaccine to prevent recurrence is planned. Clinical trial information: NCT02301611.

Abstract 6536: Safety and efficacy of autologous tumor lysate particle loaded dendritic cell (TLPLDC) vaccination in combination with systemic therapies in patients with metastatic melanoma

Abstract Background: The treatment of melanoma has changed drastically with the advent of immunotherapy, particularly checkpoint inhibition (CPI). Unfortunately, only 50-60% of tumors respond to current immunotherapy. The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine utilizes the whole antigenic panel of the patient's tumor to stimulate T-cells and may work synergistically with other immunotherapies. We have previously demonstrated both safety and efficacy of TLPLDC vaccine as adjuvant therapy for patients (pts) with resected stage III or IV melanoma who complete the primary vaccine series. Here, we describe results in pts with metastatic melanoma treated with the TLPLDC vaccine together with other approved therapies. Methods: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles which are then phagocytosed by autologous dendritic cells ex-vivo. Pts who recurred while enrolled in a randomized phase IIb trial of adjuvant TLPLDC vaccine (crossover arm) and pts with metastatic melanoma with measurable disease (MM arm) were offered TLPLDC vaccine in an open-label fashion in addition to other approved therapies as determined by their treating physician. The vaccine is given via intradermal injection monthly x4 followed by boosters at six and nine months. Tumor response is measured by RECIST 1.1 criteria. Results: To date, 53 pts have been enrolled (28 in the crossover arm and 25 in the MM arm). Within the crossover arm, 18 pts had received TLPLDC as part of the phase IIb trial, 8 were from the placebo group, and 2 patients withdrew prior to vaccination. Within the MM arm, 2 were excluded for no evidence of disease at time of vaccination and 1 withdrew. The vaccine was well tolerated, with 24% of patients experiencing a treatment-related adverse event (AE), with no grade ≥3 AE. Concurrent therapies were varied in the crossover arm, but 36% received CPI, compared with 68% in the MM arm. Of those receiving CPI, 59% had >1 immune-related AE, none of which were grade ≥3. In the crossover arm, 12-month overall survival (OS) was 83.3% in the vaccine-naïve cohort at median follow-up of 6.0 months vs. 94.7% in the re-vaccinated cohort at median follow-up of 9.0 months (p=0.961). In the MM arm, 12-month OS was 61.2% at a median follow-up of 7.7 months. In a pooled analysis of 33 evaluable pts, vaccine-naïve pts (n=21) had a 42.9% non-progression rate compared to a 66.7% non-progression rate in re-vaccinated pts (n=12). Conclusion: Vaccination with the TLPLDC vaccine in combination with approved systemic therapies in MM pts is well tolerated, with acceptable rates of immune-related AE when combined with CPI. Additionally, vaccination, and specifically re-vaccination, may provide clinical benefit particularly if used in combination with other approved therapies. Citation Format: Robert Connor Chick, Annelies T. Hickerson, Guy Travis Clifton, Phillip M. Kemp Bohan, Tommy A. Brown, Jessica L. Cindass, John W. Myers, Timothy J. Vreeland, Doreen O. Jackson, Diane F. Hale, Kaitlin M. Peace, Garth S. Herbert, Xianzhong Yu, Thomas Wagner, George E. Peoples. Safety and efficacy of autologous tumor lysate particle loaded dendritic cell (TLPLDC) vaccination in combination with systemic therapies in patients with metastatic melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6536.

Abstract 6537: Impact of disease-free interval on recurrence in high-risk melanoma patients in a phase IIb trial of the tumor lysate particle loaded dendritic cell (TLPLDC) vaccine

Abstract Background: Immunotherapy has become a mainstay of adjuvant treatment of advanced melanoma, but recurrence rates remain high. TLPLDC is a personalized vaccine that was shown in a multi-center, double-blind, placebo-controlled phase IIb trial to be safe, well tolerated, and effective for preventing recurrence in patients with resectable stage III or IV melanoma. The trial enrolled patients who had either a new diagnosis of melanoma or recurrent disease. It is hypothesized that the length of disease-free interval (DFI) may be a marker of more indolent disease and therefore a good prognostic factor for vaccine efficacy. In this study, we examined the impact of disease-free interval on response to the vaccination. Methods: Vaccine production and dosing has been described elsewhere. Patients were characterized as having either primary or recurrent disease at the time of enrollment. For recurrent patients, DFI was defined as the length of time between their initial biopsy establishing a diagnosis of melanoma and complete surgical resection. Patients were grouped by DFI into a primary and recurrent group, where the recurrent group had DFI >3 months and the primary group had no prior disease or recurrence with DFI <3 months. It is thought that a DFI of <3 months more likely represents clinically undetectable metastatic disease that was present at the time of surgical resection. Demographic data was compared using a Chi-square test and survival estimates were calculated by a Kaplan-Meier analysis. Results: Patients were randomized 2:1 (103 vaccine group, 41 control group) and divided into a recurrent group (n=48) and a primary group (n=96). There was no difference between groups in stage, age, margin status, BRAF mutation, or use of concurrent immunotherapy including checkpoint inhibitors. Patients in the recurrent group had numerically improved 24-month DFS with vaccine vs. placebo (52.6% vs. 23.5%, p=0.214) whereas the primary group had no difference (32.9% vs. 31.8%, p=0.451). Patients in the recurrent group had significantly improved overall survival with vaccine vs. placebo (94.4% vs. 50.5%, p=0.011) whereas the primary group had no difference (83.4% vs. 90.2%, p=0.779). Conclusions: The TLPLDC vaccine improved overall survival in patients with DFI >3 months prior to recurrence. These patients have more indolent disease biology and a less immunosuppressive tumor microenvironment, where monotherapy with a cancer vaccine is thought to be more effective. Further study is required to identify patients at initial presentation who are more likely to benefit from the TLPLDC vaccine. Meanwhile, combination therapy with vaccine and checkpoint inhibitor may be required for those with more aggressive disease biology. Citation Format: Robert Connor Chick, Phillip M. Kemp Bohan, Timothy J. Vreeland, Annelies T. Hickerson, Jessica L. Cindass, Diane F. Hale, Guy Travis Clifton, George E. Peoples. Impact of disease-free interval on recurrence in high-risk melanoma patients in a phase IIb trial of the tumor lysate particle loaded dendritic cell (TLPLDC) vaccine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6537.

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

63 Background: A novel vaccine strategy may prevent recurrence in high-risk melanoma patients (pts). The TLPLDC vaccine uses yeast cell wall particles (YCWP) to load tumor lysate into autologous dendritic cells (DC). In this phase IIb trial of TLPLDC vs. placebo in resected stage III/IV pts, TLPLDC increased 24 month (mo) disease free survival (DFS) in the per treatment (PT) population. Here, we present a 24mo DFS subgroup analysis and estimated overall 36mo DFS. Methods: Disease-free pts were randomized 2:1 to the TLPLDC vaccine vs. unloaded YCWP+DC at 0, 1, 2, 6, 12, and 18mo. The protocol was amended to allow concurrent adjuvant checkpoint inhibitor (CPI) therapy once approved. The pre-specified PT population included only pts completing the primary vaccine/placebo series (PVS) at 6 mo. Kaplan-Meier estimates of DFS were used to compare treatment arms by stage (III or IV) and CPI therapy (yes/no) in the ITT and PT populations. Results: 144 pts were randomized (103 TLPLDC, 41 placebo); 98 pts (66 TLPLDC, 32 placebo) completed the PVS. There were no clinicopathologic differences between treatment groups. There was no difference in 24mo DFS in stage III pts (n = 112), but in stage IV pts (n = 32), the 24mo DFS was 44% vs 0% (TLPLDC vs placebo) (p = 0.41) in ITT and 73.3% vs. 0% (HR 0.14, p = 0.002) in PT. Stage IV pts were more likely to receive CPI than stage III pts (50% vs. 30%, p = 0.003). There was no difference in 24mo DFS for pts who did not receive CPI (n = 102), but in pts who received CPI (n = 42), the 24mo DFS was 49.3% vs. 31.3% (p = 0.71) in ITT and 68.8% vs. 41.7% (HR 0.46, p = 0.28) in PT, showing a trend toward improved DFS in pts who completed the PVS and received CPI (n = 31). Overall, the 36mo estimated DFS was 34.2% vs. 21.6% (p = 0.89) for ITT and 56.9% vs. 27.9% (p = 0.021) for PT. Conclusions: The TLPLDC vaccine improved DFS in patients completing the PVS at 24 and 36 mos, particularly in the resected stage IV subset. The apparent synergistic effect with TLPLDC + CPI will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI vs. CPI alone in resected stage IV melanoma pts. Clinical trial information: NCT02301611.

Abstract CT208: Prior vaccination with the autologous Tumor Lysate Particle Loaded Dendritic Cell (TLPLDC) Vaccine may impact clinical outcomes in melanoma patients treated with systemic therapies and re-vaccination

Abstract Background: Melanoma is an immunogenic cancer, yet only 50-60% of tumors respond to current immunotherapy. The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine may potentiate an immune response by stimulating T-cells. We are conducting a phase IIb double-blinded randomized trial of TLPLDC to prevent recurrence after resection. Patients who recurred were offered enrollment in an open-label TLPLDC vaccine trial along with standard therapy. Here, we describe characteristics and clinical outcomes of recurred patients that continued on open label TLPLDC vaccination. Methods: Patients with resected no evidence of disease (NED) stage III/IV melanoma were randomized to TLPLDC vs. empty yeast cell wall particle (YCWP) loaded DC in a 2:1 fashion. TLPDC is created by loading autologous tumor lysate into YCWP. This is then introduced ex vivo to the patient’s DC for phagocytosis. 1-1.5x106TLPLDCs are given via intradermal injection monthly x4 followed by boosters at 6 and 9 months. Patients who recurred after receiving TLPLDC (vaccine group, VG) or after empty YCWP (control group, CG) on the trial (primary endpoint) were offered open label TLPLDC vaccination with same dosing schedule along with standard therapy as determined by the patient’s treatment team. Disease status is measured by RECIST criteria. Results: To date, 23 (14 VG and 11 CG) patients have enrolled and been vaccinated, with median follow up (fu) of 7.86 months (mo). The patients received the following additional therapies: surgery, gamma-knife, check point inhibitor, radiation, TVEC, BRAF/MEK, and imantinib. No related toxicities > grade 2 were observed. Of 14 VG patients, 5 were NED when re-enrolled, 9 had measurable disease (MD). Of these, 11 have followed up data, 9 (82%) show disease control (5/5 NED patients remain NED, 4/6 with MD show SD), while 2 (18%) have progressed. Of 9 CG patients, 4 were NED and 5 had measurable disease at time of re-enrollment. Of these, 8 have followed up, 5 (62%) show disease control (2/4 NED remain NED, 1/4 with MD shows regression, 2/4 SD), while 3 (38%) have progressed (2/4 NED, 1/3 with MD). Conclusion: Open label administration of TLPLPDC vaccine after recurrence is demonstrated as a safe therapy and shows potential clinical benefit when combined SOC therapy. Further study is warranted to determine if prior exposure to TLPLDC may provide clinical benefit after the first episode of disease recurrence. Citation Format: Annelies T. Hickerson, Guy T. Clifton, Tommy A. Brown, Jessica L. Cindass, John W. Myers, Timothy J. Vreeland, Diane F. Hale, Kaitlin M. Peace, Doreen O. Jackson, Garth Herbert, Xianzhong Yu, Thomas E. Wagner, George E. Peoples. Prior vaccination with the autologous Tumor Lysate Particle Loaded Dendritic Cell (TLPLDC) Vaccine may impact clinical outcomes in melanoma patients treated with systemic therapies and re-vaccination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT208.

Clinical efficacy of vaccination with the autologous tumor lysate particle loaded dendritic cell (TLPLDC) vaccine in metastatic melanoma.

e21025 Background: The treatment of melanoma has changed drastically with the advent of immunotherapy. The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine stimulates T-cells and may work synergistically with other immunotherapies. Here, we describe results in patients (pts) with metastatic melanoma (MM) treated with the TLPLDC vaccine together with other approved therapies. Methods: The TLPLDC vaccine is created using autologous tumor lysate loaded yeast cell wall particles to prime autologous dendritic cells ex-vivo. 1-1.5x106 TLPLDCs are given via intradermal injection monthly x 4 followed by boosters at six and nine months (mo). Pts who recurred while enrolled in our adjuvant phase IIb trial of the TLPLDC vaccine and pts with MM with measurable disease enrolled in a separate phase I/IIa trial were offered vaccination of TLPLDC vaccine in an open-label fashion in addition to other approved therapies as determined by their treating physician. Tumor response is measured by RECIST 1.1 criteria. Results: To date, 50 pts have been enrolled in the two trials (25 pts in each). Of the 42 pts with measureable disease, 30 pts received at least one dose of the vaccine, 11 progressed prior to vaccine administration, and 1 is pending. 2 pts withdrew at 2 and 7 mo. Of the remaining 28 evaluable pts, 13 pts had progressive disease with a median follow-up (f/u) of 3 (range 0-12) mo, 12 pts had stable disease with a median f/u of 7.5 (range 1-23) mo, 2 pts had a partial response with f/u of 7 and 13 mo, and one pt had a complete response with 18 mo of f/u. Overall, in pts with measureable disease, the disease control rate was 54% (15/28) and objective response rate was 11% (3/28). 8 pts were without measurable disease at enrollment, 3 recurred at a median f/u of 8 mo and 5 remain disease-free at a median of 26 mo f/u. No grade ≥ 3 toxicities were observed with combination TLPLDC vaccination and approved systemic therapies. Conclusions: Vaccination with the TLPLDC vaccine in combination with systemic approved therapies in MM pts is well tolerated and may provide clinical benefit in patients with and without measurable disease. Clinical trial information: NCT02678741.

Interim analysis of a prospective, randomized, double blind, placebo controlled, phase IIb trial of the TLPLDC vaccine to prevent recurrence in resected stage III or IV melanoma patients.

9525Background: The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe and immunogenic while producing objective tumor responses in a variety of met...

Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors

IntroductionTumor vaccines use various strategies to generate immune responses, commonly targeting generic tumor-associated antigens. The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from DC loaded with autologous tumor antigens, creating a patient-specific vaccine. Here, we describe initial phase I/IIa trial results. MethodsThis trial includes patients with any stage solid tumors, ECOG ≤1, and >4 months life-expectancy. A personalized vaccine is created using 1 mg of tumor and 120 ml blood (to isolate DC). Primary vaccination series (PVS) is four monthly inoculations. Patients are followed per standard of care (SOC). Endpoints include safety and tumor response (RECIST v1.1). Results44 patients were enrolled and vaccinated consisting of 31 late stage patients with residual/measurable disease, and 13 disease-free patients after SOC therapies. While 4 patients progressed before completing the PVS, 12/31 (39%) demonstrated clinical benefit (2 complete responses, 4 partial responses, 6 stable disease). In the adjuvant setting, 46% of late stage patients remain disease free at a median of 22.5 months. ConclusionsThe TLPLDC vaccine is scalable, generates a personalized DC vaccine, and requires little autologous tumor tissue and few DC. The vaccine is safe, with primarily grade 0–2 toxicities, and nearly 40% clinical benefit rate in varied tumors, warranting further study.Trial Registration: ISRCTN81339386, Registered 2/17/2016.

A prospective, randomized, blinded, placebo-controlled, phase IIb trial of an autologous tumor lysate + yeast cell wall particles (YCWP) + dendritic cells (DC) vaccine vs unloaded YCWP + DC and embedded phase I/IIa trial with tumor lysate particle only (TLPO) vaccine in stage III and stage IV (resected) melanoma to prevent recurrence.

TPS201 Background: Melanoma is a potentially lethal skin malignancy; patients with stage III/IV resected disease have a recurrence rate of 50-90%. Adjuvant checkpoint inhibitor immunotherapy decreases the risk of recurrence but also causes significant immune-related toxicity. Vaccines are a promising strategy for patients with high risk melanoma. The optimal time to intervene may be in the adjuvant setting after attaining a disease-free state through standard of care therapies. Our strategy uses autologous tumor lysate (TL) in a yeast cell wall particle (YCWP) to load dendritic cells (DC) ex vivo. The tumor lysate particle loaded dendritic cell (TLPLDC) vaccine is then given to prevent melanoma recurrences. An alternate vaccine delivery method that we are evaluating utilizes the tumor lysate particle-only (TLPO) technique, in which tumor lysate is loaded into capped YCWP and injected intradermally, allowing an in vivo uptake by the patient’s dendritic cells. Methods: We are performing a prospective, randomized, blinded, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma who have been rendered disease-free but remain at high risk of recurrence. The study will utilize the TLPLDC strategy vs placebo (2:1) in 120 patients, followed by a bridging study of TLPO vs TLPLDC (2:1) in 60 patients. Both TLPLDC and TLPO inoculations will be monthly x3, followed by boosters at 6, 12, and 18 months. Primary endpoints will be disease free survival (DFS) at 24 months in the TLPLDC arm, and overall safety in the TLPO arm. We have completed enrollment in the phase IIb portion of the study. Clinical trial information: NCT02301611.

Abstract CT036: Early trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in ovarian cancer patients

Abstract Introduction: Late-stage ovarian cancer remains difficult to treat with 1-year disease free survival rates of roughly 55% and 40% in patients (pts) with stage III and IV disease, respectively1. To date, the majority of ovarian cancer vaccines have targeted specific tumor-associated antigens with little benefit. Our vaccine approach harnesses the most potent antigen presenting cell in the body, the dendritic cell (DC), and exposes these cells to the full repertoire of tumor antigens from an individual’s cancer. Autologous tumor lysate (TL) is loaded into yeast cell wall particles (YCWP) that are naturally and efficiently taken up into the pt’s DC ex vivo. This process uses a small amount of blood and tumor and can be completed in 48 hours. The autologous TL, particle-loaded, DC (TLPLDC) vaccine is then injected intradermally (ID). This vaccine is being tested in multiple tumor types, and here we present the results in ovarian cancer. Methods: Pts with stage III or IV ovarian cancer were identified prior to surgical intervention for enrollment and tumor acquisition. Pts were treated with standard of care therapy, then enrolled in the per protocol (PP) phase I/IIa trial if disease-free or in an open label treatment registry (OTR) if they had measureable residual disease. A tumor sample (>1mg) was collected at the time of surgery, and 120mL of blood (or 50mL after a single dose of Neupogen) was drawn to isolate the pt’s DC. TL was produced through freeze/thaw cycling and loaded into YCWP, which were introduced to DC for phagocytosis; thus creating an individualized TLPLDC vaccine for each pt. Each vaccine dose contained 1x106 TLPLDC, which was injected ID in the thigh. In the PP group, the primary vaccine series (PVS) consisted of monthly vaccination x3 followed by boosters at 6 and 12 months. In the OTR, the PVS consisted of monthly vaccination x4 followed by boosters every 3 months. Pts were monitored for toxicity and recurrence or progression of disease, respectively. Results: A total of 15 pts have been treated to date, (PP: 8, OTR: 7 with 1 pt vaccinated on compassionate use). 100% of pts had successful creation of vaccine. Minimal toxicities (all ≤ grade 2) were reported. To date, in the OTR, 1 pt has shown a complete response, 1 has stable disease, and 4 have had progressive disease (PD; only 1 pt with PD completed the PVS). In the PP group, after a median follow up of 10.8 months, 3 pts (37%) have recurred (only 1 of these pts completed PVS), while 5 pts (63%) remain disease free. Conclusions: We have shown that the TLPLDC vaccine can be made efficiently (requiring only a small amount of blood, tumor and time) and is safe and well-tolerated. Our results suggest that the vaccine is better suited for the adjuvant setting rather than pts with residual disease. This data provides justification for a larger clinical trial in stage III/IV ovarian cancer pts in the adjuvant setting. 1 Kurta M, et al. Prognosis and conditional disease-free survival among pts with ovarian cancer. J Clin Oncol. 2014;32(36):4102-12. Citation Format: Kaitlin M. Peace, Timothy J. Vreeland, Guy T. Clifton, Diane F. Hale, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Mark O. Hardin, Pauline T. Nichol, Sook L. Yin, Xianzhong Yu, Thomas E. Wagner, George E. Peoples. Early trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT036. doi:10.1158/1538-7445.AM2017-CT036

A novel cancer vaccine platform utilizing autologous tumor lysate loaded into capped yeast cell wall particles.

169 Background: Our current tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine employs yeast cell wall particles (YCWP) to deliver antigen to DC ex vivo and is being tested in a randomized phase IIb trial. This strategy may be improved by injecting TL-loaded YCWP as an intradermal vaccine, with in vivo DC uptake. Silicate capping should allow YCWP to retain TL longer and stimulate DC uptake. Here, we present preclinical data on the tumor lysate, particle only (TLPO) vaccine concept vs. TLPLDC. Methods: To test the TLPO concept, YCWP were loaded with fluorescence (flr) labeled albumin and capped (cp) vs. uncapped (ucp) particles were compared for flr leak. Next, YCWP were added to cultured macrophages to evaluate DC uptake. Cells were then lysed, centrifuged, and flr in the cytoplasm vs. organelles measured. 3 C57B mice were then injected with 100ml NaCl, 106empty cp YCWP, or 1mcg GM-CSF. 5 hours (hr) post-injection, 100ml NaCl was injected into the same site, withdrawn, and examined via microscope to count monocytes. TLPO was compared to TLPLDC in a B16 murine melanoma survival model. Finally, 4 grey horses with equine melanoma were treated with autologous TLPO, injected biweekly for 4 vaccinations. Target lesions were assessed over 6 months. Results: Compared to ucp YCWP, cp had decreased flr leak at 1 (15.8% vs. 24.7%) and 2 hr (6.7% vs. 16.6%), increased uptake by DC (2hr flr readings 11065 vs. 3928) and higher delivery to DC cytoplasm (68.9% vs. 48.8%). Empty cp YCWP showed increased recruitment of monocytes (276/hpf) vs. GM-CSF (55/hpf) or NaCl alone (18/hpf). In the B16 murine melanoma model, the median survival time in days was 21 for controls (n=5), 42 for TLPLDC (n=10), and 56 for TLPO (n=20). At 6 months, the equine model revealed 1 complete and 3 partial responses (50%, 68%, and 45% tumor reduction). Conclusions: Silicate capping of the YCWP effectively limits leakage of contents, improves uptake by DC and delivery to the cytoplasm without the need for GM-CSF. In early animal studies, TLPO appears to have equivalent efficacy to TLPLDC, but eliminates the need for in vitro DC loading. We plan to perform a bridging study comparing TLPO to TLPLDC after enrollment is complete in our phase IIb TLPLDC melanoma trial.

Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors.

3089Background: Tumor vaccines use various strategies to generate immune responses, commonly targeting specific and purported tumor-associated antigens instead of antigens unique to a patient’s tum...