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Biomedical subjects

R K Oldham

Publications and source records attributed to R K Oldham.

At least 37 records · Page 2Linked to original sources
PubMed1995

Interleukin-15 and the growth of tumor derived activated T-cells.

Interleukin-15 was tested to determine whether this recently discovered cytokine was capable of stimulating the growth of tumor derived activated T cells in culture (TDAC, also referred to as tumor infiltrating lymphocytes). When established cultures of IL-2 induced, IL-2 dependent TDAC were tested, IL-15 stimulated growth in a dose dependent manner, alone or in the presence of IL-2. One established TDAC was cultured with IL-15 alone for 18 passages over a 10 week period. Comparing IL-2 and IL-15 treated cultures, growth rate with IL-15 was slower. IL-15 doubled the secreted interferon alpha and granulocyte-macrophage colony stimulating factor. IL-15 and IL-2 were compared in primary TDAC cultures. IL-15 induced TDAC outgrowth in 3 of 6 cultures. IL-2 induced outgrowth in all 6. Tumor cells were eliminated as TDAC grew out in both IL-2 and IL-15 treated cultures. These results suggested that IL-15 like IL-2, is capable of stimulating the growth of TDAC with antitumor activity, but with certain distinct effects which may be of interest therapeutically.

Humans↗
PubMed1995

Interferon alpha-2a and external beam radiotherapy in the initial management of patients with glioma: a pilot study of the National Biotherapy Study Group.

The National Biotherapy Study Group conducted a phase I/II trial of alpha-interferon (IFN) plus radiation therapy (RT) in glioma patients to confirm the feasibility of combining these two modalities. Patients newly diagnosed gliomasreceived external beam RT as 180 cGy in 33 fractions over six to seven weeks, five days a week, and IFN at a dose of 3 MIU SC Monday, Wednesday and Friday of each week. IFN was increased to 5 MIU after two weeks and was given for up to 16 weeks. Patients were monitored for toxicity and failure-free and overall survival. There were 12 men and seven women with an age range of 24-77, and a median age of 64 years. There were 12 glioblastomas and seven advanced astrocytomas. Complete surgical resection was carried out in two patients, nine had a partial resection, and eight had a biopsy only. Two patients in the latter group deteriorated rapidly and received < 2 weeks of RT/IFN. One patient stopped IFN because of a skin rash, another stopped because of concurrent pneumonia, and one patient was noncompliant. RT and IFN were well-tolerated; 14 of the 19 patients completed the eight weeks of IFN/RT. However, only three patients took IFN for the maximum of 16 weeks. The only grade 4 toxicities noted were increases SGOT in three, increases alk phos in two, and severe fatigue in four patients. The median failure-free survival was two months, median survival was 7.5 months, and four patients survived beyond one year. The longest survivor was 29.1 months, and one patient is still alive after 20.7 months. IFN/RT can be safely co-administered in patients with gliomas. A randomized trial would be needed to establish clinical benefit.

Adult↗
PubMed1994

Growth of tumor derived activated T-cells for the treatment of cancer.

This report describes the production of Tumor Derived Activated Cell cultures (TDAC, also called tumor infiltrating lymphocytes) from patient tumor biopsies and our preliminary experience growing these cells to therapeutic levels using artificial capillary bioreactor cultures. TDAC were successfully grown in medium containing Interleukin 2 from 80% of the 113 tumor biopsies tested. There was no significant difference in success (growth to 1 x 10(9) cells) comparing primary and metastatic tumors. Many of the tumors were shipped to the laboratory from distant sites. Success rate did decrease with the length of time for tumor transport. Interleukin 4 was beneficial in the development of 1 of 4 TDAC cultures which did not grow with IL-2 only. Seventy-seven bioreactor cultures were initiated for 31 patients. On the average, 1.9 x 10(9) TDAC were inoculated per bioreactor; 3.3 x 10(10) were harvested in 22 days. Twelve liters of medium were required per 1 x 10(10) TDAC produced. TDAC cultures contained T cells with variable ratios of CD4 to CD8 cells. Secreted granulocyte monocyte colony stimulating factor, interferon gamma and tumor necrosis factor were measured in the bioreactor cartridge conditioned medium. Twenty three patients were evaluated. Partial responses were observed in 4 patients including a dramatic remission of scalp nodules in a patient with renal cancer. Results showed that therapeutic amounts of TDAC cells may be produced in a reasonable and cost effective manner using artificial capillary bioreactor cultures.

Biopsy↗
PubMed1993

Inpatient continuous-infusion interleukin-2 in 788 patients with cancer. The National Biotherapy Study Group experience.

BACKGROUND: Interleukin-2 (IL-2), used alone or in combination with adoptive cellular therapy, is one of the most promising biologic therapeutic agents for cancer treatment. METHODS: The National Biotherapy Study Group conducted 15 trials of continuous-infusion IL-2 involving 788 patients with cancer, 638 of whom were evaluable for tumor response. The protocols included administration of IL-2 and lymphokine-activated killer (LAK) cells, IL-2 and cyclophosphamide, IL-2 and tumor-infiltrating lymphocytes, IL-2 and alpha-interferon (IFN), IL-2 and tumor necrosis factor, and IL-2 and LAK alternating with combination chemotherapy. RESULTS: Responses were detected in 33 of 188 patients (18%) with melanomas, 13 of 167 (8%) with renal cell carcinomas, and 1 of 76 (1%) with colorectal cancers. The median survival times in patients with melanoma and renal cell cancer were 9.6 and 9.3 months, respectively. The proportion of patients surviving 1 year were 35% and 43%, respectively. There were responses in 8 of 51 patients (16%) with lung cancer, but many of these patients received IL-2 and LAK alternating with platinum-based chemotherapy. Four of 23 patients (17%) responded who had breast cancer and received IL-2 and IFN. The protocols involving IL-2 plus adoptive cellular therapy produced a higher response rate than those not involving activated cells (48 of 312 [15%] versus 24 of 326 [7%], P = 0.003); however, there was no difference in survival. There was a 1.8% mortality rate attributed to the complications of IL-2 itself. CONCLUSIONS: IL-2 produces durable tumor responses in some patients, especially in those with melanoma and renal cell carcinoma. Because the drug's toxicity is significant and the overall response rates are low, patient selection may be the most important factor in the clinical use of continuous-infusion IL-2 therapy.

Adolescent↗
PubMed1993

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Delivery of Health Care↗
PubMed1992

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Peer Review↗
PubMed1992

Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial.

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.

Adult↗
PubMed1991

Continuous interleukin-2 and tumor-infiltrating lymphocytes as treatment of advanced melanoma. A national biotherapy study group trial.

Melanoma metastases were harvested from 82 patients for the purpose of growing and expanding tumor-infiltrating lymphocytes (TIL). Tumor tissue cell suspensions were incubated with interleukin-2 (IL-2), followed by repeated exposure to tumor antigen with or without OKT3 monoclonal antibody (MoAb). Initial growth success was achieved in 56 of 82 cultures (72%). Efforts were made to expand 26 of these 56 cultures for therapeutic TIL; 23 of 26 early cultures (88%) were successfully expanded for in vivo therapy. It took a mean of 78.5 +/- 25.4 days to grow sufficient TIL for treatment. Therapy included cyclophosphamide (1 g/m2) on day 1, followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/d) on days 2 to 5, and approximately 10(11) (mean 1.49 +/- 0.93 x 10(11)) TIL on day 2. Patients who responded received monthly IL-2 as a 96-hour infusion. Median patient age was 45 years of age. Sixty-seven percent of the patients were men. Performance status was 0 to 1 in 77% of patients. Thirty-four percent of the patients had liver metastases. The usual IL-2 toxicities were seen. Response rate for 21 patients was 24% (95% confidence interval, 10% to 49%). One complete response was achieved with cells 98% CD4+; four partial responses were achieved with cells 80%, 94%, 98%, and 98% CD8+, respectively. Four of eight patients who received TIL, which had never been stimulated with OKT3, had tumor response. The authors conclude that a treatment plan for IL-2/TIL is technically difficult, costly, and effective for only a minority of patients. Overall, clinical results are not clearly superior to those obtained with other IL-2 regimens.

Adult↗