International Society for Biological Therapy for Cancer: 20th Anniversary

Dillman, Robert O MD

From the Hoag Cancer Center, Newport Beach, California.

Received for publication February 28, 2005; accepted March 8, 2005.

Dr. Dillman is Past President of the International Society for Biological Therapy for Cancer, Past President of its Executive Council, and a two-term Board Member.

Reprints: Robert O. Dillman, MD, Medical Director, Hoag Cancer Center, One Hoag Drive, Bldg. 41, Newport Beach, CA 92658 (e-mail: rdillman@hoaghospital.org).

The November 10-13, 2005, annual scientific meeting of the International Society for Biologic Therapy for Cancer (iSBTc) will mark the 20th anniversary of this annual meeting and, in a sense, the Society itself. From its inception, the Society has had the mission to facilitate the exchange of scientific information about and to promote the use of biologic therapies for cancer. The organization was founded in 1984 by Robert K. Oldham, MD, who had served as the first director of the NCI's Biologic Response Modifier Program (BRMP), centered in Frederick, Maryland. The first conceptual organizational meeting for the Society took place at the 1983 spring meetings of the American Association for Cancer Research (AACR) and the American Society for Clinical Oncology (ASCO), in San Diego, with the 40 charter members listed in Table 1. Enthusiasm for such a society emanated from the promising scientific breakthroughs in recombinant DNA technology, monoclonal antibody technology, and tumor immunology. There was a sense that we were on the verge of a technological revolution that would lead to a new pipeline of systemic therapeutic products that would complement and/or supplant chemotherapy in the treatment of cancer. From its inception, the organization was intended to have a balance of members from academia, government, and industry, and clinical as well as basic scientists, with an emphasis on taking the new biotherapy technologies from the bench to the bedside.

Table 1

TABLE 1. Charter Members of the Society for Biological Therapy

LEADERSHIP OF THE SOCIETY

Past presidents of the Society are listed in Table 2. Dr. Oldham became the first president of the Society, serving from 1984 to 1986. All of the presidents have been trained as medical oncologists, other than Michael T. Lotze, MD, a surgical oncologist. In 2003 Ulrich Keilholz, MD, from Berlin, became the Society's 11th president and the first president from outside the United States. The strategic planning for the organization is derived from a Board of Directors that has grown over the years from six to nine at-large members, in addition to the current officers of the organization. At present, three new at-large members are elected each year by the membership to serve 3-year terms that overlap 2-year terms of two different presidents.

Table 2

TABLE 2. Past Presidents of the iSBTc

A list of prior board members is shown in Table 3. Presidents are elected for 2-year terms from a slate of candidates derived from the Board of Directors. In recent years, the election has been in the form of an election for a 2-year term of a vice president, who is also president-elect. The immediate past president remains on the Board of Directors for an additional 2 years. Thus, typically presidents now are directly involved in the leadership of the Society for up to 9 consecutive years, including 3 as at-large board members and 6 more in the presidential succession process. After that they become members of an executive council of past presidents that serves in an advisory capacity to the president and vice president and therefore indirectly to the Board of Directors. Because of the tremendous growth of the group during 2000 to 2004, efforts are in progress to develop a stronger committee structure led by board members.

Table 3

TABLE 3. Members of the Board of Directors of the iSBTc

EVOLUTION OF SCIENTIFIC MEETINGS

Table 4 lists the geographic sites and organizers for the annual scientific meetings that have taken place under the banner of Society for Biological Therapy (SBT) and the iSBTc. Many of the charter members of the Society were involved in the First Conference on Immunity to Cancer, chaired by Malcolm Mitchell, MD, and Arnold Reif, MD, in Williamsburg, Virginia, in the fall of 1984. The success of that meeting encouraged the Society to proceed with plans for an annual meeting of the Society of Biological Therapy. Programs from the early meetings included only invited speakers, but the meetings soon evolved to include plenary and keynote speakers, invited oral presentations, oral presentations of submitted abstracts, and poster sessions.

Table 4

TABLE 4. Sites and Organizers for the Annual Scientific Meetings of the iBSTc

The content of the meetings has reflected the contemporary key research areas in biologic therapy. The first meeting under the auspices of the Society was held in Chapel Hill, North Carolina, in the fall of 1986. It featured presentations on a variety of promising cytokines, including interferon alpha, which had become the first biological to receive FDA approval for a malignant indication, hairy cell leukemia; interleukin-2, which would be approved in the spring of 1992 for the treatment of renal cell carcinoma; and several hematopoietic colony-stimulating factors that would come into standard clinical use during 1989 to 1991. The Second Conference on Immunity to Cancer, also chaired by Dr. Mitchell, attracted more than 300 attendees to Williamsburg, Virginia, in the fall of 1987 for a meeting co-sponsored by the Biologic Response Modifiers Program and the Division of Cancer Treatment of the NCI and the SBT. Subsequent meetings were organized and sponsored by the Society with varying support from the biotechnology industry and the NCI. Typically, meeting topics have focused on potential product development, including the vast number of anticancer vaccine strategies, active specific immunotherapy, adoptive cellular therapies, including lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TILs), and donor lymphocyte infusion therapy, in association with nonmyeloablative allogeneic transplants (cytokines from IL-1 to IL-27), and monoclonal antibodies and immunoconjugates. In recent years there have been numerous sessions on immune monitoring, angiogenesis, and the tumor environment, as well as tumor biology and mechanisms of tumor resistance to biologic therapies.

Changes in the format of the meeting have evolved. A Presidential Award (plaque and cash prize) for the best abstract submitted by young investigators was initiated at the 1991 Pittsburgh meeting at the suggestion of Ronald Herberman, MD, co-organizer of the meeting and later a president of the Society. The top papers, as chosen by the program committee, submitted by young investigators are presented in a Presidential Plenary Session and the best paper is then selected by a small committee that typically includes the president-elect, president, and immediate past president. Table 5 lists the past winners of the Presidential Award. Jon Wigginton, MD, who won the Presidential Award at the 1995 Williamsburg meeting, is president-elect for the 2006-2008 term. At the suggestion of Dr. Lotze, organizer of the 1998 Pittsburgh meeting and later president, a pre-meeting primer that included reviews of tumor immunology and the status of biologic therapy in cancer treatment was added. Under the leadership of future presidents Michael Atkins, MD, and Dr. Keilholz, the 2000 meeting in Bethesda included a highly successful workshop on immune monitoring. Subsequent meetings have included similar workshops. Because of the growth in membership and meeting size, meetings in the new millennium have included concurrent sessions in addition to the plenary sessions. The high attendance at the workshops and primer meetings have resulted in 3.5-day meetings, taking place from Thursday to mid-Sunday.

Table 5

TABLE 5. Young Investigator Presidential Award Winners

EVOLUTION OF THE SOCIETY

1986-1991

The early vision of the founders was that the Society would evolve into a organization of clinical practitioners who specialized in the administration of biologic therapy. It was felt that the Society would ultimately succeed in the same manner as ASCO. The potential for chemotherapy as a therapeutic modality had resulted in the establishment of the medical oncology subspecialty and the creation of ASCO as a society within AACR. The increasing success of chemotherapy in clinical practice led to tremendous growth in ASCO membership and eventually separation from the annual meeting of AACR. Optimism regarding the potential for biotherapy products resulted in increasing attendance at the Society's meetings by medical oncologists during 1987 to 1990. Dr. Oldham had founded the National Biotherapy Study Group (NBSG), which became the Cancer Biotherapy Research Group (CBRG), and many of its physicians and nurses attended these early meetings. The first four presidents had all been heavily involved with the formation or early operation of the BRMP. During this time, the Board endeavored to maintain the momentum that accompanied this optimism for a clinically significant impact from biologic agents, although at the same time many laboratory researchers felt their role in the Society was underappreciated.

Dr. Oldham also established the Journal of Biologic Response Modifiers, published by Raven Press, and served as its editor; the cover was pink, with a burgundy title. He endeavored to have this become SBT's official journal. In 1990 Steven A. Rosenberg, MD, became the new editor, and the name was changed to the Journal of Immunotherapy. The cover color was changed to green, and the size increased to the standard 8.5 × 11.5 inches. The Board decided to have the journal as the official publication of the Society but did not make paid subscription a requirement and benefit of membership. Overtures to the American Board of Internal Medicine to create a certification process for a subspecialty of practitioners to deliver biologic therapy were rejected. During this era, the Society was administered through the clerical support of the various presidents and secretary-treasurers. The major biotechnology companies from this era were Schering-Plough and Roche, who had marketed interferon alpha; OrthoBiotech and Amgen, who co-marketed erythropoietin; and Amgen, who developed and marketed granulocyte colony-stimulating factor (G-CSF).

1992-1998

The increasing complexity of regulatory compliance and lack of approved therapeutic biologic products meant that the content of the meetings was more often focused on preclinical work and phase 1 and 2 trials rather than phase 3 trials or optimizing the use of approved biologicals in anticancer therapy. In November 1993, the FDA announced in the Federal Register and New England Journal of Medicine that all biologicals, including patient-specific products that involved modification of the tissue, would require an Investigational New Drug (IND) approval by the agency. This wording allowed processing of hematopoietic stem cells from peripheral blood or tissue without an IND but implied that autologous cell products that were exposed to tissue culture incubation would require an IND. This greatly limited the ability to conduct trials with patient-specific products such as adoptive cell therapy with TILs or LAK cells or autologous tumor cell vaccines. The slow introduction of biologic products and the rapid growth of medical oncology allowed the few therapeutic products to be readily integrated into the medical oncology specialty rather than into a separate specialty devoted to biologic therapy. The fifth president, Michael Hawkins, MD, and the SBT board declared that the focus of the Society would be at the translational level of preclinical and phase 1 trials. In 1995, David Parkinson, MD, became editor of the Journal of Immunotherapy, and Raven Press was acquired by Lippincott. The journal continued as the official journal of the Society.

This narrowed focus, combined with limited clinical progress in the field, the decline in support from the biotechnology industry following declines in the stock market, and disillusionment caused by failure of large numbers of putative therapeutic biologicals to make it into the clinic, resulted in an exodus of practicing oncologists from the Society. Remaining were a core of physicians committed to clinical investigation of biologic therapies and an ever-evolving group of basic scientists developing biologic therapies and exploring such therapies in animal models. In hindsight, perhaps the most important trend in this era was that between May 1992 (approval of interleukin-2) and November 1997 (approval of rituximab), no new therapeutic biologic products were approved by the FDA. The largest attendance at an annual meeting of the Society during this era was 151 (the 1994 Napa, California, meeting). Active membership in the Society and meeting attendance declined and reached its nadir at the 1995 and 1997 meetings in Williamsburg, Virginia, and Pasadena, California, which attracted fewer than 100 attendees. Another difficulty in this period was an indirect consequence of two of the Society presidents during this era being physically located at the NCI, where restrictions were placed on their degree of active leadership of the Society. Because of the increased restrictions on and uncertainty of administrative support from the NCI or industry, Richard Smalley, MD, who had been the third president, stepped forward to administer the group through his own cancer research company, Synertron, Inc. He functioned as secretary-treasurer from 1994 to 1998, during which time he registered the Society as a not-for-profit corporation in Wisconsin. The only biotechnology company that succeeded with approval of a therapeutic biologic product in this era was Cetus, later acquired by Chiron, which received approval for interleukin-2 in 1992; however, this agent was not readily embraced by the practicing medical oncology community. The Society experienced declining attendance at its meetings in 1997 and 1998, which were associated with a loss of $60,000.

1999-2005

The Society's 1994 meeting, held at Silverado in Napa, California, featured a presentation by Anthony Grillo-Lopez, MD, from the small San Diego biotech company IDEC. He described a 47% response rate in lymphoma for a chimeric anti-CD20 monoclonal antibody in a multicenter phase 2 trial. This study, later published with 1993 Presidential Award winner David Maloney, MD, as lead author, confirmed the phase 1 single-institution activity for this product, which Dr. Maloney also had published. After completion of pivotal trials, in 1997 that agent was approved by the FDA as rituximab (Rituxan), the first monoclonal antibody approved specifically for the treatment of human malignancy. Even though its use was limited to CD20-positive B-cell malignancies, in its first year of sales rituximab set a record for a new cancer agent, surpassing the previous record that had accompanied introduction of the chemotherapy agent paclitaxel. This monoclonal antibody has become the most important single agent in the treatment of B-cell malignancy and now generates revenues of over $1 billion a year, shared by Biogen-IDEC and Genentech. This blockbuster financial success rekindled enthusiasm for biologic therapy, which increased over the next few years following the approval of a number of monoclonal antibodies and similar biologic products (Table 6). There are now 17 biologic products approved for the treatment of cancer in the United States; 10 were approved during 1997 to 2004 (Fig. 1). Genentech had two additional products approved in this era (trastuzumab and bevacizumab), and Biogen-IDEC added one (Y-90 ibritumomab tiuxetan). This era also saw small biotech companies develop products that could be manufactured only with a larger partner, resulting in marketing partnerships between IDEC and Genentech (rituximab), ILEX and Berlex (alemtuzumab), and Corixa and GlaxoSmithKline (I-131 tositumomab). A number of other biologic products, which are used in the management of cancer patients but not specifically approved for cancer marketing indications, are not included in Figure 1. Examples include immunoglobulin preparations, gamma interferon, antithymocyte globulin, anti-CD3 monoclonal antibodies, and the anti-CD25 monoclonal antibody daclizumab (originally developed as an agent for T-cell leukemia but approved for marketing only to prevent kidney transplant rejection).

Figure 1

FIGURE 1. Total cumulative numbers of biologic products for cancer therapy approved by the FDA, 1986 to 2004.

Table 6

TABLE 6. Biological Agents Approved by the FDA for Use in the Treatment of Cancer

The renewed enthusiasm for biologic therapy carried over into the vaccine field, where many laboratories and investigators had continued to pursue approaches with autologous tumor cells, autologous tumor cell lines, allogeneic cell lines, and peptide antigens that had been identified by cytotoxic T-cell responses. Another reason for renewed optimism for vaccine approaches was the increased understanding of the antigen-presenting role of dendritic cells and reproducible methodologies for their production. It was hoped that combining one or more of these antigen sources with dendritic cells would finally result in successful vaccine strategies. This renewed enthusiasm for vaccine strategies has been associated with increased meeting attendance at the same time that the commercial success of biologic products has led to increased support from the biotechnology and pharmaceutical industries.

A number of administrative and organizational changes began under the leadership of Dr. Lotze, who took office following the 1998 meeting in Pittsburgh. This included reaffirmation that immunotherapy is only one facet of biologic therapy, expansion of the Board, establishment of a 6-year hegemony from president-elect to president to immediate past president, internationalization of the Society, and creation of an executive council of past presidents. The responsibilities for administering the group passed from Dr. Smalley to a meeting planning organization, ProED, Inc. Unfortunately, a somewhat overambitious effort to support an American and European meeting in the same year created what was almost a financial disaster. At the Seattle meeting in November 2000, the incoming president was confronted with the resignation of ProED as the Society's administrative management group and a Society that was more than $70,000 in debt. One of the first actions during the term of Robert O. Dillman, MD, was a contractual agreement with a new management group, Executive Director Incorporated (EDI), located in Milwaukee, Wisconsin. Thanks to the administrative efficiency of Tara Withington and her staff and the tremendous fundraising efforts spearheaded by future president Dr. Atkins, the group was able to climb out of debt quickly and become financially stable.

During Dr. Dillman's term the bylaws were modified, the name was officially changed from the Society for Biological Therapy to the International Society for Biological Therapy for Cancer, and the Society was again incorporated in Wisconsin with updated bylaws. The addition of international and cancer to the name reflected the globalization of the Society and affirmed the focus on cancer; which had been there from inception of the Society. In 2000, Dr. Rosenberg returned to the role of editor-in-chief for the Journal of Immunotherapy, and the journal's cover color was changed to blue. In 2001 the Board voted to include the Journal of Immunotherapy as part of membership, which resulted in an increase in annual dues but strengthened the relationship between the Society and the journal. The editor-in-chief and all associate editors and the editorial board are now active members of the iSBTc. With the year-round administrative assistance of EDI staff members, highly successful meetings attracting more than 400 attendees and expanded membership quickly ensued. Lee Murray, MD, of M. D. Anderson led a successful membership committee that increased the number of dues-paying members. During Dr. Atkins' presidency there was further growth in meeting attendance to more than 500 attendees and a further increase in financial reserves. He also convened a planning meeting to map out a strategic plan for the future. A key component of this plan is an expanded committee structure to expand leadership of the organization.

2006-2012

The iSBTc is about to embark on a new era. Technological and commercial globalization is a reality. The international aspect of the Society has been affirmed with the succession to the presidency of Dr. Keilholz. Efforts to expand international membership are in progress. The Society needs to expand and retain its membership to sustain the financial reserves that are needed to increase benefits to members. There is a need to attract young clinical and laboratory investigators into the Society and retain their membership as they progress in their careers. The Society must sustain the balance between clinical and laboratory investigators who can communicate with one another to sustain translation of the research to the clinic, and the participation of investigators based in academic, government, industry, and regulatory settings. The Society must retain the participation and support of the biotechnology industry, which is largely dependent on the regulatory approval and clinical success of products that emerge from the translation of the research. At the moment there are large numbers of vaccine products in advanced stages of testing. The commercial success or failure of these products may have a profound impact on the Society, just as the failure to commercialize adoptive cellular therapy or monoclonal antibodies during the early 1990s was associated with a decline in the Society. However, as shown in Figure 1, it is apparent that the expectation for a sustained biotechnology pipeline of effective anticancer products has been met and should continue for the foreseeable future.

ACKNOWLEDGMENTS

Source documents used in preparation of this manuscript included past program proceedings, minutes of the Board of Directors, and the Society newsletters authored by the late Richard V. Smalley, MD. The author acknowledges the suggestions and helpful recollections of Robert K. Oldham, MD, Ernie Borden, MD, Michael Mastrangelo, MD, and Malcolm Mitchell, MD, PhD.

© 2005 Lippincott Williams & Wilkins, Inc.