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Dillman R.O.,Hoag Institute for Research and Education | Dillman R.O.,Hoag Family Cancer Institute | Cornforth A.N.,California Stem Cell | Depriest C.,Hoag Institute for Research and Education | And 6 more authors.
Journal of Immunotherapy | Year: 2012

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 μg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy. Copyright © 2012 by Lippincott Williams & Wilkins.


Dillman R.O.,Hoag Institute for Research and Education | Dillman R.O.,Hoag Family Cancer Institute | Dillman R.O.,Cancer Biotherapy Research Group | Depriest C.,Cancer Biotherapy Research Group | And 2 more authors.
Cancer Biotherapy and Radiopharmaceuticals | Year: 2014

Various published data show that in patients with metastatic melanoma, high-dose interleukin-2 (IL2) is associated with 5-year survival rates of 15% from treatment initiation. We previously reported a median survival of 15.6 months, and a 20% 5-year survival rate for 150 patients who were treated with inpatient IL2 (Cancer Biother Radiopharm 2012;27:337). In the current study, we sought to determine whether treatment with active specific immunotherapy (ASI) with patient-specific tumor stem cell vaccines derived from autologous tumor cell (TC) lines contributed to the survival result. Existing databases revealed that 32/149 IL2-treated patients also received ASI, while 117 did not. ASI was given within 12 months of IL2 therapy in 19/32 patients. Patients who received IL2 plus ASI had better overall survival (p<0.001) with longer median survival (39.5 vs. 12.0 months) and a higher 5-year survival rate (39% vs. 13%). Survival was better even after exclusion of 55 IL2-alone patients who died before 12 months of follow-up (p=0.12). In subset analyses, survival was longer for 25 patients who received ASI after IL2 than for 7 who received ASI before IL2 (5-year survival 46% vs. 14%, p<0.001) and for 16 patients who received a dendritic cell/TC-based ASI compared with 16 injected with irradiated TC (p=0.17). This retrospective study suggests that receipt of IL2 followed by a patient-specific melanoma stem cell vaccine is associated with better survival than IL2 alone. © Mary Ann Liebert, Inc.


Hanna D.L.,University of Southern California | Hanna D.L.,Hoag Family Cancer Institute | Lenz H.-J.,University of Southern California
Expert Review of Clinical Pharmacology | Year: 2016

Although the survival of metastatic colorectal cancer (mCRC) patients has improved five-fold over the last century, CRC remains a significant global health burden. Impressive strides have been made in identifying new regimens, employing maintenance strategies to limit treatment toxicities, and combining multidisciplinary approaches to achieve cure in oligometastatic disease. Attempts at personalized integration of targeted agents have been limited by the ability to identify molecularly enriched patient populations most likely to benefit. In this review, we discuss novel therapeutics and regimens recently approved and in development for mCRC. In addition, we discuss using older agents in novel combination and maintenance strategies, and highlight evidence for implementing pharmacogenomic data and non-invasive monitoring into the personalized management of mCRC patients. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Dillman R.O.,Hoag Institute for Research and Education | Dillman R.O.,Hoag Family Cancer Institute | McClure S.E.,Hoag Institute for Research and Education
Clinical Lung Cancer | Year: 2014

Background National data demonstrate minimal improvement in survival for patients diagnosed with lung cancer despite a number of apparent advances during the past 3 decades. We wished to know how demographic characteristics, staging, therapy, and survival have changed over time for patients with lung cancer who were accessioned to the cancer registry of a large community hospital in southern California.Patients and Methods Clinical features and survival data were collected on patients diagnosed during each of the successive 6-year eras of 1986 to 1991 (n = 812), 1992 to 1997 (n = 1072), 1998 to 2003 (n = 1209), and 2004 to 2009 (n = 1365).Conclusion Survival has steadily improved for patients in this community who were diagnosed with lung cancer. The explanations for this improvement are multifactorial, but include earlier stage at diagnosis, decreases in histologic types associated with active smoking, and increased use of systemic therapies.Results Median survival improved from 11 to 13 to 16 to 26 months and overall 5-year survival steadily improved from 16.5% to 19.1% to 24.0% to 31.1%. The proportion of patients with localized disease at diagnosis increased from 18.4% to 24.1% to 24.9% to 31.6%. Improvements in relative survival were much greater than have occurred nationally. Other obvious trends over time were increasing age of patients, increasing proportions with diagnoses of adenocarcinoma with concomitant decreases in squamous cell and small cell histologies, and decreases in the proportion of large cell carcinoma with reciprocal increases in neuroendocrine diagnoses. The use of chemotherapy for patients with local disease tripled in the most recent era. © 2014 Elsevier Inc.


Hepatic metastases from melanoma are usually associated with recurrence and short survival, even in patients with a solitary metastasis. Two patients, one with melanoma of unknown primary and one with ocular melanoma, underwent resection of a solitary liver metastasis followed by treatment with eltrapuldencel-T, a patient-specific therapeutic vaccine consisting of autologous dendritic cells loaded with antigens from irradiated melanoma cells obtained from an autologous tumor cell line. Following surgical resection, the ocular melanoma patient remained progression free for more than 4.5 years and was known to be alive more than 8.5 years later, while the other patient, who previously had experienced lung and small bowel metastases, has remained disease free and is alive more than 12 years later. These two cases illustrate how immunotherapies designed to induce immune responses to tumor-associated antigens (TAA), as opposed to releasing previously existing responses to TAA that have been suppressed, may also enhance long-term disease control and survival. © Copyright 2016, Mary Ann Liebert, Inc.


PubMed | Hoag Family Cancer Institute
Type: Case Reports | Journal: Cancer biotherapy & radiopharmaceuticals | Year: 2016

Hepatic metastases from melanoma are usually associated with recurrence and short survival, even in patients with a solitary metastasis. Two patients, one with melanoma of unknown primary and one with ocular melanoma, underwent resection of a solitary liver metastasis followed by treatment with eltrapuldencel-T, a patient-specific therapeutic vaccine consisting of autologous dendritic cells loaded with antigens from irradiated melanoma cells obtained from an autologous tumor cell line. Following surgical resection, the ocular melanoma patient remained progression free for more than 4.5 years and was known to be alive more than 8.5 years later, while the other patient, who previously had experienced lung and small bowel metastases, has remained disease free and is alive more than 12 years later. These two cases illustrate how immunotherapies designed to induce immune responses to tumor-associated antigens (TAA), as opposed to releasing previously existing responses to TAA that have been suppressed, may also enhance long-term disease control and survival.

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