Children's Cancer Research Foundation Research Articles

Abstract B38: Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells

Abstract Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone-marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1 specific allorestricted T-cell receptor (TCR) wild-type and transgenic cytotoxic (CD8+) T cells against ES. Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide specific allorepertoire-derived (i.e., allorestricted) CD8+ T cells. Patient #1 received up to 4.8 x 105/kg body weight HLA-A*02:0 allorestricted donor-derived wild type CD8+ T cells. Patient #2 received up to 8.2 x 106/kg HLA-A*02:01 donor-derived and patient #3 up to 6 x 106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319). Findings: HLA-A*02:01/CHM1319 specific allorestricted CD8+ T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft-versus-host disease (GVHD). Patients #1 and #3 showed slow progression, whereas patient #2, while having BM involvement, showed partial metastatic regression associated with T-cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks. Interpretation: HLA-A*02:01/antigen specific allorestricted T cells proliferate in vivo without causing GVHD. CHM1319 TCR transgenic T cells home to affected BM and are associated with partial disease regression. Funding: Wilhelm Sander-Stiftung (2006.109.1), Else Kröner-Stiftung (GR & SB; P31/08//A123/07), BMBF (GR, UT and SB, TranSarNet 01GM1104B; SB, PROVABES 01KT1311) and Cura Placida Children's Cancer Research Foundation. PHS is funded by the Excellenzinitiative at TUM/CCC Munich. Citation Format: Uwe Thiel, Sebastian J. Schober, Ingo Einspieler, Andreas Kirschner, David Schirmer, Katja Gall, Oxana Schmidt, Thomas G. P. Grunewald, Poul H. Sorensen, Guenther H. S. Richter, Irene Teichert von Luettichau, Dirk H. Busch, Stefan Burdach. Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B38.

Mrs. Professor

Mrs. Professor

The Blout Laboratory at Harvard Medical School from 1957 to 1972

Elkan R. Blout's laboratory at the Children's Cancer Research Foundation and Harvard Medical School pioneered many approaches to the synthesis, conformation and structural studies of polypeptides, biopolymers and selected proteins. Here the early days (1957-1972) of his research group are remembered.

A tribute to Sidney Farber – the father of modern chemotherapy

Sidney Farber, world-renowned paediatric pathologist, made major contributions to his field but is acknowledged as the father of the modern era of chemotherapy. He recognised that folic acid stimulated leukaemic cell growth and enhanced disease progression. He hypothesised that folic acid antagonists would inhibit or arrest the proliferation of cancer cells. His landmark study, published in 1948, demonstrated that a number of folic acid antagonists, including 4-aminopteroyl-glutamic acid (aminopterin) produced temporary remissions in children with acute undifferentiated leukaemia. These observations lead to the development and use of other chemotherapeutic agents, either singly or, more effectively, in combination for treating childhood and adult malignancies. He introduced actinomycin D for the treatment of metastatic and localised Wilms tumour. Under his guidance and leadership, both the 'Jimmy Fund', one of the first comprehensive paediatric oncology treatment centres, and the Children's Cancer Research Foundation, which later became the Dana-Farber Cancer Institute, were founded.

Bilateral wilms' tumor

Twenty children with bilateral Wilms' tumor presented to the Children's Hospital Medical Center and Children's Cancer Research Foundation, Sidney Farber Cancer Institute, and Joint Center for Radiation Therapy (CHM-CCCRF, SFCI, JCRT) from January 1, 1956 to December 31, 1976. Of these 20, 16 had simultaneous and 4 had metachronous disease on presentation. All patients were treated with surgery, radiation and chemotherapy. Of the 16 patients with simultaneous disease, 10 (63%) are alive and free of disease 12+ to 175+ months post diagnosis and treatment, with median follow-up of 121 months. There were no long-term survivors in the metachronous group; all were dead of disease within 21 months from initial presentation of original tumor. With these data we relate prognosis to extent of disease and discuss a general approach to the mangement of bilateral Wilms' tumor.

Studies of Aggregates of Two Muscle Proteins with Scanning Transmission and Conventional Transmission Electron Microscopy

Studies of the structures of various aggregates of proteins from vertebrate striated muscle have begun, using in particular the scanning transmission electron microscope (STEM). The high collection efficiency of this microscope has been noted elsewhere and the contrast advantage and signal selection capabilities have been demonstrated.Although the instrument can produce high contrast images of unstained and unfixed biological material, it is not clear which preparation methods might maintain the native structure of such material. So the study begins on familiar ground with conventionl negatively stained preparations, While later steps will include less conventional methods.Rabbit tropomyosin Mg-tactoids in suspension were received from Dr. Carolyn Cohen (of Children's Cancer Research Foundation, Boston). The tactoids have a primary periodicity of 395 Å. Isolated myofibrils were obtained from Joseph Etlinger (of this University); myosin was extracted from them by a method similar to that of Dow and Stracher.

HEAD AND NECK TUMORS IN CHILDREN

This report is a review of 178 children with malignant head and neck tumors seen during a ten-year period at the Children's Hospital Medical Center and the Children's Cancer Research Foundation in Boston, Massachusetts. Each tumor type is analyzed to display its unique features. When a neck mass occurs, a complete ENT examination is needed to identify an occult primary in the nasopharynx, in the nose, or in some other site that is difficult to see. A total physical examination is needed to detect a systemic disease or a primary below the clavicle. Many of the tumors of the head, unfortunately, are internal and present with common symptoms, like an earache, a stuffy nose, or a headache. They only become identified when the tumor greatly enlarges or metastasizes. Treatment with surgery, cryosurgery, radiation therapy, and chemotherapy may be used alone or in various combinations of them.

Epidemiology of acute myelomonocytic leukemia in children.

Acute myelomonocytic leukemia was diagnosed in 73 children at the Children's Cancer Research Foundation and the Children's Hospital Medical Center in Boston, 1949–1971. Although the disorder may occur within the first year of life, no association was found with inherited disorders or with prenatal exposure to potential carcinogens. Three patients had a well-documented history of antecedent aplastic anemia, suggesting that prolonged myelodepression is an etiologic factor or precursor state in myelomonocytic leukemia. In addition, eight others appeared to have antecedent anemia, thrombocytopenia, or pancytopenia for months to years, a finding previously described in adults with myelomonocytic leukemia.

Interferon and cell division. VII. Inhibitory effect of highly purified interferon preparations on the multiplication of leukemia L 1210 cells.

SummaryHighly purified mouse interferon preparations prepared by different techniques in different laboratories inhibited the mul–tiplication of mouse leukemia L 1210 cells. The dose–response curves of the antiviral activity of interferon and the anticell multiplication activity using a sensitive assay were parallel. Likewise, the kinetics of the appearance of the factor responsible for both activities and the curves of thermal inactiva–tion of this factor were also parallel. It seems reasonable to conclude that interferon itself can inhibit cell multiplication.I. G. is deeply indebted to Dr. Sidney Farber, Director of the Children's Cancer Research Foundation, Boston, MA for his continued interest and support. K. P. acknowledges the aid of NSF Grant No. G. B.–26515. M. T. is the recipient of an EMBO fellowship.

COMPARATIVE DIFFRACTION STUDIES ON MYELIN MEMBRANES.

Annals of the New York Academy of SciencesVolume 195, Issue 1 p. 309-320 COMPARATIVE DIFFRACTION STUDIES ON MYELIN MEMBRANES* D. A. Kirschner, D. A. Kirschner Laboratory of Structural Molecular Biology Children's Cancer Research Foundation and Harvard Medical School Boston, Massachusetts 02115Search for more papers by this authorD. L. D. Caspar, D. L. D. Caspar Laboratory of Structural Molecular Biology Children's Cancer Research Foundation and Harvard Medical School Boston, Massachusetts 02115Search for more papers by this author D. A. Kirschner, D. A. Kirschner Laboratory of Structural Molecular Biology Children's Cancer Research Foundation and Harvard Medical School Boston, Massachusetts 02115Search for more papers by this authorD. L. D. Caspar, D. L. D. Caspar Laboratory of Structural Molecular Biology Children's Cancer Research Foundation and Harvard Medical School Boston, Massachusetts 02115Search for more papers by this author First published: June 1972 https://doi.org/10.1111/j.1749-6632.1972.tb54811.xCitations: 36 * This work has been supported by United States Public Health Service grant CA04696 from the National Cancer Institute, and by a Postdoctoral Fellowship to D.A.K. from the National Multiple Sclerosis Society. The research carried out at Brookhaven National Laboratory was under the auspices of the United States Atomic Energy Commission. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume195, Issue1Membrane Structure and its Biological ApplicationsJune 1972Pages 309-320 RelatedInformation

Objectives and problems of developing and operating cancer centers

CancerVolume 29, Issue 4 p. 825-825 ArticleFree Access Objectives and problems of developing and operating cancer centers Sidney Farber MD, Sidney Farber MD Chairman President and Director, Children's Cancer Research Foundation, Boston, Mass.Search for more papers by this author Sidney Farber MD, Sidney Farber MD Chairman President and Director, Children's Cancer Research Foundation, Boston, Mass.Search for more papers by this author First published: April 1972 https://doi.org/10.1002/1097-0142(197204)29:4<825::AID-CNCR2820290406>3.0.CO;2-0 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume29, Issue4April 1972Pages 825-825 RelatedInformation

Acute Childhood Leukemia: Epidemiologic Study by Cell Type of 1,263 Cases at the Children's Cancer Research Foundation in Boston, 1947–65

Acute Childhood Leukemia: Epidemiologic Study by Cell Type of 1,263 Cases at the Children's Cancer Research Foundation in Boston, 1947–65

Treatment of metastatic colorectal carcinoma with 5-fluorouracil by mouth.

CancerVolume 28, Issue 4 p. 902-906 ArticleFree Access Treatment of metastatic colorectal carcinoma with 5-fluorouracil by mouth S. R. Lahiri MD, Corresponding Author S. R. Lahiri MD Adult Tumor Therapy Division of Children's Cancer Research Foundation and Dept. of Medicine, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Mass. Research Associate, Children's Cancer Research Foundation, Jr. Associate in Medicine, Peter Bent Brigham Hospital, Instructor in Medicine, Harvard Medical School.Chief, Dept. of Oncology, Wesson Memorial Hospital, 140 High St., Springfield, Mass. 01105===Search for more papers by this authorG. Boileau MD, G. Boileau MD Adult Tumor Therapy Division of Children's Cancer Research Foundation and Dept. of Medicine, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Mass. Research Associate, Children's Cancer Research Foundation, Jr. Associate in Medicine, Peter Bent Brigham Hospital, Instructor in Medicine, Harvard Medical School.Search for more papers by this authorT. C. Hall MD, T. C. Hall MD Adult Tumor Therapy Division of Children's Cancer Research Foundation and Dept. of Medicine, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Mass. Professor of Medicine and Pharmacology, University of Rochester School of Medicine and Dentistry, 260 Crittenden Blvd. Rochester, N.Y.Search for more papers by this author S. R. Lahiri MD, Corresponding Author S. R. Lahiri MD Adult Tumor Therapy Division of Children's Cancer Research Foundation and Dept. of Medicine, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Mass. Research Associate, Children's Cancer Research Foundation, Jr. Associate in Medicine, Peter Bent Brigham Hospital, Instructor in Medicine, Harvard Medical School.Chief, Dept. of Oncology, Wesson Memorial Hospital, 140 High St., Springfield, Mass. 01105===Search for more papers by this authorG. Boileau MD, G. Boileau MD Adult Tumor Therapy Division of Children's Cancer Research Foundation and Dept. of Medicine, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Mass. Research Associate, Children's Cancer Research Foundation, Jr. Associate in Medicine, Peter Bent Brigham Hospital, Instructor in Medicine, Harvard Medical School.Search for more papers by this authorT. C. Hall MD, T. C. Hall MD Adult Tumor Therapy Division of Children's Cancer Research Foundation and Dept. of Medicine, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Mass. Professor of Medicine and Pharmacology, University of Rochester School of Medicine and Dentistry, 260 Crittenden Blvd. Rochester, N.Y.Search for more papers by this author First published: 1971 https://doi.org/10.1002/1097-0142(1971)28:4<902::AID-CNCR2820280413>3.0.CO;2-RCitations: 38 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume28, Issue41971Pages 902-906 ReferencesRelatedInformation

Establishment of lines from normal human blood leukocytes by co-cultivation with a leukocyte line derived from a leukemic child.

SummaryWhite blood cells from a normal adult male regularly became established as continuous lines when cultured in the presence of X-irradiated cells of an EBV-infected line of leukocytes derived from a leukemic girl and a monolayer of human placental cells. Seven of the 9 lines thus established became infected with EBV. The possible role of the various components of the culture system in the observed transformation is discussed.Note added in proof: The TNL line in Expt. 1, which did not demonstrate EBV antigen at the time the manuscript was submitted, showed approximately 0.4% cells with antigen when it was subsequently examined.We are grateful to the Children's Cancer Research Foundation for clinical specimens and to Mrs. A. von Zweck, Miss A. Holloway, Miss E. Grogan, Mrs. I. Irwin and Mrs. E. Lisco for valuable assistance.

Paravertebral "round cell" tumors in children.

Arecent review of the records of the Division of Radiotherapy, Children's Hospital Medical Center, and of the Children's Cancer Research Foundation of Boston has disclosed 5 patients who had a malignant neoplasm which appeared to be unusual because of its histologic characteristics and its clinical course in relation to the site of origin at diagnosis. In each child, the epidural space of a portion of spinal cord was involved and the adjacent paravertebral soft tissues were infiltrated to varying degrees. Symptoms of cord compression were due to extradural pressure. Except for a congenital abnormality of a vertebral body, one patient exhibited no radiographic evidence of bone alteration at the local site. The other patients were found to have radiographic changes in the neural arch of a vertebral body at the site of tumor involvement. These changes were due to pressure by extrinsic tumor and secondary bone reaction. Case Reports CASE I: M. K., a girl, was born with a lumbar hemivertebra at L-2 and resulta...

WILMS' TUMOR AND CONGENITAL HEMIHYPERTROPHY: REPORT OF FIVE NEW CASES AND REVIEW OF LITERATURE

Among 225 patients with Wilms' tumor seen at the Children's Cancer Research Foundation in Boston, 7 had congenital hemihypertrophy (a frequency of 1:32), bringing to 26 the number of cases reported in the literature with this association. In one child the cytogenetic study of leukocyte cultures revealed elongation of the long arms of both No. 16 chromosomes; each parent and two of four siblings had a similar anomaly affecting one chromosome of pair 16. Dermatoglyphics on this patient and three others in the series were unremarkable, as were studies of urinary gonadotropin excretion. From a review of all cases reported with Wilms' tumor and hemihypertrophy, little was found to indicate a relationship to other disorders, such as Silver's syndrome or neurofibromatosis, in which hemihypertrophy has been described. A role of inheritance was suggested in our series by one patient who had a sibling with hemihypertrophy, the seventh reported familial occurrence of this congenital defect. From the sparse evidence available, it would appear that the origins of hemihypertrophy are heterogeneous and include genic, chromosomal, and other factors which are presently obscure. The association between hemihypertrophy and Wilms' tumor may reflect common etiologic factors or a pre-neoplastic anlage in "hemihypertrophic" kidneys. Since hemihypertrophy seems to be related also to childhood neoplasms originating in the adrenal cortex and liver, further research on this anomaly should enhance our understanding of oncogenic mechanisms.

Melanoma as a Medical Problem

Malignant [ALIGNANT melanoma continues to be an enigmatic disease and, judging from the large number of studies in the recent literature,^1-10of wide clinical interest as well. Yet, few authors have attempted to validate clinical description of their cases by statistical methods. Nor has any report appeared detailing results of medical treatment of a large number of patients. The purpose of this report is to summarize such data on the natural history and therapy of the disease on the basis of 164 patients seen at the Children's Cancer Research Foundation between 1947 and 1966. <h3>Incidence Factors</h3> As reported in the literature, melanoma represents only 1% to 3% of malignant tumors^11,12but an average of 14% of the adult tumor clinic population at the Children's Cancer Research Foundation have this disease. Sixty-seven percent of our patients were observed until death, 24% are alive, and 9% have been lost to

Radiotherapeutic management of testicular neoplasms in children.

Primary tumors of the testicle are not common in childhood. (3, 5, 11–13, 17, 23, 29, 36, 43). A review of the records of all children less than sixteen years of age at the Children's Hospital Medical Center from 1930 to 1965 and at the Children's Cancer Research Foundation revealed 21 cases of primary malignant tumor of the testicle. In our experience, this comprises approximately 1 per cent of malignant neoplasms in childhood. An additional 5 cases of benign testicular neoplasms have also been recorded. Malignant Tumors of Germ-Cell Origin Embryonal-Cell Carcinoma: Fifteen of the 21 malignant tumors were classified as embryonal-cell carcinoma. Two additional cases were classified as teratoma with embryonal-cell carcinoma (J. O. and C. S., Table I). The age at diagnosis ranged from six months to nine and a half years, with an average of two years and five months. The duration of symptoms before diagnosis ranged from three days to thirty months, with an average of five months. Initial therapy consisted of total excision of the affected testicle and the spermatic cord in all patients but one (J. M., Table I). Further surgical management was instituted in 8 patients, 6 of whom underwent retroperitoneal node dissection in continuity with dissection of the iliac nodes on the affected side. In one patient (R. W.) these areas were explored, but only a limited dissection of the lymph nodes was carried out; and in another (J. O.) the ipsilateral iliac lymph nodes were excised up to the level of the aortic bifurcation but no dissection above this level was performed. All these patients had lymph nodes histologically negative for tumor. Seven of the 8 patients had further therapy: irradiation to the retroperitoneum and pelvis. Six of the 8 patients with more extensive surgery never evidenced dissemination and remain free of disease. In 2 solitary pulmonary metastases developed, with control attained at four and two years, respectively. In the first patient (R. S.), the testicular mass was first aspirated without surgical extirpation. After his referral to The Children's Hospital Medical Center, radical orchiectomy and combined retroperitoneal and iliac node dissection were followed by irradiation to the sites of node dissection. Six months thereafter, a solitary metastasis developed in the left upper lung field. In the second patient with pulmonary metastasis (D. G.), biopsy of the testicular mass was followed one week later by a simple orchiectomy. After his referral to the Children's Hospital Medical Center, surgical extirpation of the spermatic cord on the affected side was carried out, together with retroperitoneal and iliac node dissection. Irradiation was then administered. It was eight months later that a solitary lesion developed in the right upper lung field. In each case 1,200 rads were delivered in eight days to the total volume of both lung fields. The dose to the local area was increased to a total of 2,000 rads in twelve days. Complete response to therapy was noted in each patient (Figs. 1 and 2), and both are alive and well at four and two years, respectively.

18. Comparison of various agents as protective agents against freezing injury of platelets: Isaac Djerassi,* Albert Roy, Sidney Farber,* John Cavins, and Edmund Klein* (Children's Cancer Research Foundation and The Department of Pathology, Harvard Medical School, at The Children's Hospital, Boston, Massachusetts)

18. Comparison of various agents as protective agents against freezing injury of platelets: Isaac Djerassi,* Albert Roy, Sidney Farber,* John Cavins, and Edmund Klein* (Children's Cancer Research Foundation and The Department of Pathology, Harvard Medical School, at The Children's Hospital, Boston, Massachusetts)

43. An animal model for the study of frozen human normal and leukemic white blood cells: Albert Roy, Isaac Djerassi,* Sidney Farber,* Raymond Vaillancourt,* and John Cavins (Children's Cancer Research Foundation and The Department of Pathology, Harvard Medical School, at The Children's Hospital, Boston, Massachusetts)

43. An animal model for the study of frozen human normal and leukemic white blood cells: Albert Roy, Isaac Djerassi,* Sidney Farber,* Raymond Vaillancourt,* and John Cavins (Children's Cancer Research Foundation and The Department of Pathology, Harvard Medical School, at The Children's Hospital, Boston, Massachusetts)